Primary Aldosteronism

EPIDEMIOLOGY
Primary aldosteronism was first described by Jerome Conn in 1955.3 The clinical characteristics and manifestations, frequently referred to as Conn’s syndrome, include hypertension, hypokalemia, hypernatremia, and alkalosis with increased urinary potassium excretion and decreased urinary sodium. Many patients with aldosteronism exhibit certain forms of diabetes.1
The most common cause of primary aldosteronism is a solitary aldosterone-secreting adrenal adenoma. However, there are a large group of patients who will exhibit primary aldosteronism as a result of bilateral focal or nodular adrenal hyperplasia. In addition, a few patients have been reported with aldosteronism as a manifestation of adrenocortical carcinoma; the syndrome may be exaggerated in these rare instances. In children, aldo-steronoma is rare, with most cases secondary to adrenocortical hyperplasia.
PATHOPHYSIOLOGY
The electrolyte and acid–base disorders of aldosteronism are readily understood as a consequence of excessive production of aldosterone. However, the exact mechanism of the hypertension, generally indistinguishable from essential hypertension, is not easily explained. On the other hand, hypertension in the presence of hypokalemia (serum potassium less than 3.5 mEq/liter), alkalosis (serum bicarbonate more than 30 mEq/liter), and hyperkaluria (urinary excretion of more than 30 mEq/24 hr) is most certainly caused by aldosteronism. The diagnosis can be confirmed by measurement of plasma aldosterone levels, remembering that there will be a diurnal variation and postural responses. A more reliable method of establishing elevated aldosterone levels is the measurement of 24-hour urinary excretion values (normal range 5 to 19 µg/24 hr).10
DIAGNOSIS
Laboratory

The routine laboratory determinations noted above are fundamental to the diagnosis of primary aldosteronism. Measurement of plasma and urinary aldosterone can generally be accomplished in hospital and commercial laboratories. Adrenal venous sampling for measurement of plasma adosterone is almost always accurate in determining elevated levels of aldosterone as well as aiding in the localization of solitary adenomas.
The postural stimulation test (PST) may be used not only to confirm the diagnosis of primary aldosteronism but also to distinguish between aldosterone-producing adenoma and idiopathic hyperplasia as the cause of the syndrome. Serum aldosterone and cortisol levels are measured after overnight recumbency, patients are ambulated for 4 hours, and the tests are then repeated. Patients with adenoma exhibit elevated base levels of aldosterone that will either fall or increase minimally after upright activity, whereas the high base level of aldosterone in patients with hyperplasia will generally rise signficantly, more than 30%. Demonstration of a reduced or unchanged cortisol after ambulation confirms the validity of the test, reflecting the usual morning fall in ACTH.
Further diagnostic confirmation of primary aldosteronism may be gained through measurement of plasma renin.4 Renin production is suppressed, usually below normal levels, in aldosteronism as compared with renin levels in normal subjects or those with hypertension of other causes. This is the consequence of the homeostatic mechanism by which blood volume and hence blood pressure is maintained under normal circumstances. Figure 3-1 graphically depicts this mechanism in which a decreased blood volume or flow to the kidney stimulates the stretch receptor mechanism, invoking increased production of renin. Renin then acts on angiotensin I to convert it to angiotensin II, which in turn stimulates adrenocortical production of aldosterone. This generates increased excretion of urinary potassium with conservation of sodium, leading to fluid retention, which, in turn, increases the blood volume. Clearly, the presence of increased aldosterone will lead to some degree of hypervolemia, which will result in decreased production of renin.
Aldosteronoma may also be differentiated from idiopathic hyperplasia by serum assay for 18-hydroxycorticosterone (18-OHB). Young and Klee10 observed that patients with adenoma usually have 18-OHB levels more than 100 ng/dl after overnight recumbency, whereas patients with hyperplasia have values less than 100 ng/dl. It has been reported that 18-OHB assay accuracy is increased by intravenous saline infusion, and it has also been observed that the ratio of 18-OHB to cortisol is greater than 3 in patients with aldosteronoma but not in patients with hyperplasia.
The diagnosis of primary aldosteronism may be confirmed or excluded using the fluorocortisone (0.1 mg q6h for 4 days) suppression test. Similarly, familial hyperaldosteronism type 1 may be diagnosed or excluded by use of the dexamethasone (0.5 mg q6h for 4 days) suppression test, although identification of the hybrid gene in peripheral blood DNA may also be diagnostic.
Localization Techniques
A variety of imaging techniques may be employed for localization of aldosterone-producing adenomas or adrenal hyperplasia, though actual adrenal enlargement with patients with focal micronodular hyperplasia is uncommon. Large adrenal tumors greater than 3.0 cm in diameter may be visualized on a plain film of the abdomen or by intravenous pyelography. However, it is extremely unusual for aldosterone tumors of the benign type to present as a large mass. In contrast, the rare malignancy may achieve significant size.
In years past, retroperitoneal carbon dioxide insufflation studies were employed for visualization of the adrenals. This invasive technique is no longer necessary because both CT scanning and magnetic resonance imaging are extremely effective in identifying hyperplastic adrenals or aldosterone-producing adenomas as small as 6 or 7 mm.6 The anatomic relationship of the adrenal glands to the kidneys or other viscera as delineated by CT or MRI is illustrated in Fig. 3-2.
Adrenal venography is not recommended as a routine procedure. The retrograde injection of contrast material into the adrenal may produce an infarction on occasion. If such injury is incurred by the normal adrenal, removal of the contralateral adrenal with an aldosteronoma could result in adrenal insufficiency. However, adrenal venography may be accomplished on some occasions, particularly if adrenal vein hormone sampling is desired.
Adrenal scintigraphy is one of the most useful noninvasive studies in functional evaluation and anatomic localization of aldosteronomas.5 Adrenocortical scanning is performed with the radionuclide 131I-6-b-iodomethyl-19-norcholesterol (NP-59). All antihypertensive medications should be discontinued for 1 week, allowing normal dietary sodium intake with the addition of dexamethasone treatment for 3 to 7 days. Oral iodide is given to block tracer uptake by the thyroid, and imaging is performed 2 to 5 days after administration of NP-59. Prompt unilateral adrenal uptake and activity are evidence of aldosteronoma, whereas bilateral uptake is evidence of adrenal hyperplasia. The test has about a 75% accuracy.
INDICATIONS FOR SURGERY
It is imperative that the cause of primary aldosteronism be established because the etiology will determine treatment and management.7 Patients with adrenal carcinoma most certainly should have adrenalectomy, preferably by open surgery and usually through the transabdominal approach. Patients with idiopathic hyperplasia as a cause of aldosteronism are best managed medically because surgical removal of the adrenals rarely will result in control of hypertension. Medical management consists of administration of spironolactone, diuretics such as hydrochlorothiazide, and antihypertensive medications if necessary.
Removal of a discrete aldosteronoma will result in cure of hypertension and conversion of biochemical abnormalities in 80% to 90% of patients. Accordingly, adrenalectomy or partial adrenalectomy is the procedure of choice in patients with an aldosterone-producing adenoma. Because bilateral and ectopic aldosteronomas are essentially unheard of, the unilateral removal of the adenoma or the adrenal is preferred.
ALTERNATIVE THERAPY
It must be stated that aldosterone-producing adenomas of the adrenal are essentially ideal for laparoscopic management.2 This technique is amply described in Chapter 132. Laparoscopic adrenalectomy will become the procedure of choice for the single adenoma producing aldosteronism, but there will be instances in which open surgery is desirable.9
SURGICAL TECHNIQUE
General endotracheal anesthesia is required. Position of the patient demands control of the airway, and forceful ventilation at times during the procedure is necessary for identifying and protecting the diaphragm and pleura and in closing any pleural rents that may be incurred during the exposure. There are no special anesthetic requirements, such as nitroprusside, as with pheochromocytoma.
The preferred approach to the involved adrenal in cases of primary aldosteronism secondary to adenoma is posterior (Fig. 3-3). Incision may be the classical hockey stick, as described by Hugh Hampton Young, or a rib incision may be utilized. Personal preference is for an oblique incision over the 11th rib, resecting the rib as far medially as possible but preserving the periosteum, which affords excellent substance for closure. An alternative is the supracostal incision of Turner-Warwick, cutting the rib at its posterior angle to allow for inferior deflection. The supracostal incision avoids the infracostal vessels and nerves. Personal preference is for rib resection (Fig. 3-4).
Entry into the pleural cavity can be avoided by carefully reflecting the pleura upward. This is best accomplished by beginning the dissection laterally at the extreme lateral margin of the incision. By blunt and sharp dissection, the pleura and most of the diaphragmatic muscle fibers can be swept medially and superiorly, literally moving the pleural cavity away from the diaphragm to give access to the retroperitoneal space. By using this technique and proceeding from lateral to medial, it is usually possible to avoid entry into the pleural cavity.
Once the retroperitoneal space has been entered, Gerota’s fascia can be identified. This should be opened as far superiorly as possible. The perinephric fat is readily identified, having slightly different texture than the surrounding retroperitoneal fat deposits. The peri-nephric fat is dissected medially and superiorally to expose the upper pole of the kidney, which is then freed of surrounding fat. A padded Deaver rectractor is then introduced over the upper pole of the kidney, which is retracted inferiorly. This maneuver will almost always bring the ipsilateral adrenal into view in the operative field.
The adipose tissue surrounding the adrenal is delicately teased away from the adrenal gland. No significant vasculature is encountered in this dissection, but small bleeders may be controlled by electrocautary. The adrenal is thoroughly exposed before an attempt is made to gain access to the vessels.
The blood supply of the adrenals is variable from side to side and from patient to patient. It is relatively independent of renal circulation (Fig. 3-5). The arterial supply to each adrenal consists of a multitude of small branches derived from the renal artery, the aorta, the inferior phrenic, and occasionally from the splenic artery on the left. The venous return is much more constant than the arterial supply, the right adrenal vein arising from the hilum of the gland medially and emptying directly into the vena cava, whereas on the left, the main adrenal vein joins the inferior phrenic to empty into the left renal vein. Control of the vasculature is generally achieved with small metal surgical clips as the dissection proceeds.
Injury to contiguous structures must be avoided. On the right, the adrenal is in close proximity to the liver superiorly and anteriorly, the vena cava medially, and the kidney inferiorly. Great care should be taken to identify the vena cava because the gland is in intimate contact. On the left, the adrenal is somewhat closer to the renal pedicle, and care must be taken in exposing the inferior surface of the gland to prevent damage to the renal artery and vein. The posterior aspect of the stomach and the tail of the pancreas are in close approximation to the left adrenal anteriorly.
Once the gland has been isolated, it is removed from the wound, and the bed is inspected for bleeding, which is controlled by cautery in most instances. Occasionally it is useful to employ a square of Gelfoam or Oxycel in the bed of the adrenal. Surgical drains are unnecessary in virtually all cases. When retraction is discontinued, the kidney will ascend into its normal position, virtually obliterating the space from which the adrenal gland was removed.
Gerota’s fascia is closed using multiple running and interrupted sutures of absorbable materials, usually catgut or polyglycolic acid (PGA). Closure of the rib bed consists of approximating the two portions of the periosteum with either absorbable or nonabsorbable suture material, usually 2-0 catgut, taking care to avoid injury to the infracostal neurovascular bundle.
There is scanty musculature overlying the rib, but this may be closed with interrupted absorbable sutures. Subcutaneous tissue is approximated with running or interrupted plain catgut, and skin may be closed with metal clips or, preferably, with interrupted vertical mattress sutures of 3-0 silk.
With the imaging studies available, aldosterone tumors will almost always have been localized preoperatively. Rarely, it may be necessary to accomplish bilateral adrenal exploration before making a decision about adrenalectomy. If this is the case, simultaneous and identical exposures of the adrenal area may be achieved. The Finochietto thoracic retractor may be utilized with the blades reversed to compress the paraspinialis musculature in the fashion shown in Fig. 3-6.
OUTCOMES AND COMPLICATIONS
Entry into the pleura occurs with great frequency simply because of the deep inferior reflection in many patients. Indeed, such entry into the pleural cavity cannot be regarded as a complication but rather as the anatomic consequence in most instances. Opening into the pleura can be managed near the conclusion of the case. A soft rubber catheter of about 18 F caliber with multiple openings cut near its tip is introduced into the pleural cavity. The pleura with diaphragm is then closed with running sutures incorporating the catheter. The anesthesiologist is requested to fully expand the lungs for a period of about 30 seconds while suction is applied to the catheter, which is then quickly withdrawn, and the suture is tied securely while the lung is inflated. A postoperative chest x-ray obtained in the recovery room will assure that there is no residual pneumothorax.
Intraoperative bleeding is virtually never a problem. On the left, the aorta is readily identified by palpation of its pulsation, which permits avoiding any injury in dissection. A bit more caution must be employed on the right because the vena cava is not as readily identified. If the vena cava is opened during the process, it is best closed with running suture of atraumatic 3-0 vascular silk.
Variations in blood pressure during surgery are rarely encountered. Whereas the patient with pheochromocytoma may experience wide fluctuations in blood pressure, the hypertensive patient with aldosteronism does not exhibit this same lability. As a consequence, preventive measures such as administration of blood volume expanders or whole blood are rarely necessary.
Postoperative infection is also a rarity in surgery for aldosteronoma. Although the patient with Cushing’s disease may suffer immune suppression and a tendency to infection, this is not the case in primary aldosteronism. Ordinarily, prophylactic postoperative antibiotic therapy is not employed, but an elderly person with poor ventilation and potential pulmonary compromise may justify utilization of anticipatory antibiotic therapy.
Early ambulation is optimal. To facilitate patient mobility, a Marcaine block of the intercostal nerves attendant to the resected rib and the ribs above and below the line of incision may be useful.
A simple dry dressing is applied in the operating room but may be removed the day after surgery. Discharge can be effected on the second postoperative day in some cases.
The most significant complication of surgery of aldosteronism is the persistence of hypertension. This is common in patients with idiopathic adrenal hyperplasia but uncommon in patients who have a solitary adenoma as the etiology of aldosteronism.8
If a normal adrenal gland is present contralaterally, there should be no problem with adrenal insufficiency. However, in congenital absence of the opposite adrenal, supplemental corticosteroids and mineralocorticoids will be necessary.

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