Cushing’s Disease and Syndrome

The association of pituitary lesions in patients with hirsutism, proximal muscle weakness, round plethoric faces, increased supraclavicular and infrascapular fat pads, thin skin, and other less frequent signs such as acne, purple abdominal striae, and psychiatric symptoms (Cushing’s syndrome) has been known as Cushing’s disease since the original description relating the illness to pituitary lesions by Cushing in 1912. It was many years later that the syndrome was found to be caused by cortisol excess, and later still it was found that there were multiple etiologies for this excess, including ectopic production of ACTH in adrenal tumors and tumors arising in other organs, including some that may be ectopic sources for corticotropin-releasing factor.
The first planned operation for adrenal tumor was performed in 1914, with removal of a 17-cm adrenal adenoma and subsequent cure of hyperadrenocorticism. Initial attempts at curative pituitary surgery for Cushing’s disease were short lived for lack of the necessary technology, but with modern microsurgical techniques, transsphenoidal pituitary microsurgery has become the treatment of choice. Adrenal surgery for Cushing’s syndrome has in the past varied from partial to total adrenalectomy, depending on the availability of supplemental glucocorticoids.
The etiologies of Cushing’s syndrome are summarized in Table 1-1 and Fig. 1-1. In general, the pathophysiology of these disorders involves the production of excessive ACTH from pituitary adenomas or from ectopic sources, benign adrenal tumors and macronodular and micronodular adrenal hyperplasia, which usually produce excessive glucocorticoids only, whereas many adrenal malignancies also produce excessive androgens and mineralocorticoids. Iatrogenic administration of glucocorticoids is also a common etiology of Cushing’s syndrome.
DIAGNOSIS
The sine qua non for the diagnosis of Cushing’s syndrome is an abnormality of the plasma or urinary cortisol and/or ACTH. Because these studies are extremely variable, sometimes fluctuating daily and frequently negative, a high degree of suspicion usually leads the clinician to evaluate the patient with an overnight dexamethasone suppression test, a metapyrone stimulation test, or corticotropin-releasing factor stimulation. Imaging studies such as CT scanning, adrenal arteriography and venography, MRI (with and without gadolinium), and scintigraphy have also been used with some success. Because of the lack of sensitivity and specificity of these studies, it would also be common to perform repetitive evaluations in many patients.
INDICATIONS FOR SURGERY
Indications for surgery of the adrenal gland in patients with Cushing’s syndrome include adrenal adenoma, adrenal hyperplasia, and adrenal carcinoma. Bilateral adrenalectomy has been suggested for those patients with micronodular adrenal hyperplasia, macronodular hyperplasia, patients with unknown sources of ACTH, and those with incurable pituitary Cushing’s syndrome.3,6
ALTERNATIVE THERAPY
Treatment of the aforementioned causes of Cushing’s disease all require surgical management except for the iatrogenic administration of glucocorticoids.
SURGICAL TECHNIQUE
The posterior approach to the adrenal glands is described here; the other surgical approaches to the adrenals are described in Chapter 2, Chapter 3, Chapter 4 and Chapter 132. The posterior approach to the adrenal gland was first described by Young in 1936. Most authors would reserve this technique for small adrenal adenomas or adrenal hyperplasia, i.e., noncancerous states with small lesions.1,6 It is also the ideal method for bilateral adrenal exploration because the patient does not have to be repositioned. The patient is placed in the prone position under general endotracheal anesthesia. Appropriate padding is used to pad the chest, anterior pelvis, and legs (Fig. 1-2).
Several incisions have been described, and we prefer the hockey-stick incision, which begins just lateral to the midline at the ninth or tenth rib and extends downward and then laterally over the 11th or 12th ribs. Alternatively, an 11th rib incision or supracostal incision is used.4,6 In the supracostal incision, the rib is spared, the intercostal muscles are divided, the pleura is swept away from the rib, and the retroperitoneum is entered (Fig. 1-3). In the other approaches, the latissimus dorsi and sacrospinalis muscles are divided and retracted medially. The incision is extended through the periosteum of the 12th rib, which is resected close to the vertebral body (Fig. 1-4). The deep periosteum is incised, avoiding the neurovascular bundle, while laterally the abdominal muscles are divided and the pleura dissected from the diaphagm, exposing Gerota’s fascia. As an alternative, in the transthoracic approach, the exposed pleura and diaphragm are incised, again exposing Gerota’s fascia. It should be noted that the decision on which rib space to utilize (10, 11, or 12) depends on the position of the adrenal as estimated by the imaging studies, and it would be rare to be too high with the placement of the incision. In bilateral adrenalectomy, a Finochetti retractor can be placed for exposure (Fig. 1-5).
Gerota’s fascia is incised, and the perinephric fat is swept away or incised superiorly, exposing the adrenal. Inferior retraction3,6 of the kidney aids this portion of the dissection (Fig. 1-6). On the left side, the resection of the adrenal proceeds from laterally and superiorly to medially and inferiorly, where the main veins are ligated, the largest draining into the renal vein while the major adrenal artery arises from the main renal artery. On the right, the dissection is similar, but care is taken medially where the short right adrenal vein (and occasional accessory veins) empties into the vena cava. The largest adrenal artery usually arises from the main renal artery.
If the pleura is entered, a temporary “pull-out” Robinson catheter (14 to 18 F) is placed, the pleura sutured, and the musculature approximated. While deep inspiration is maintained by the anesthesiologist, and the catheter is placed in an underwater seal, the catheter is quickly removed after all air bubbling in the water ceases. The remainder of the wound closure is completed, and a dressing applied.
OUTCOMES
Complications
Surgical complications following adrenal surgery for Cushing’s syndrome include not only those that pertain to routine retroperitoneal surgery, e.g., blood loss and infection, but also those complications specific to patients with hormonal imbalances. It should be mentioned that a chest x-ray in the recovery room is essential after any flank surgery in which the patient has been placed in the lateral or prone position, to evaluate the patient’s pulmonary status for atelectasis and/or pneumothorax when the pleura has been violated. The occurrence of adrenocortical insufficiency should be kept uppermost in the clinician’s mind even in the patient who has had a unilateral adrenalectomy. The use of supplemental glucocorticoids and mineralocorticoids is commonplace in these complex patients, whereas those in whom adrenalectomy is not curative need further evaluation, looking for ectopic sites of disease, either benign or malignant. Postoperative wound healing may be impaired, and the infection rate has been described to be between 4% and 21%. Other complications, e.g., thromboembolism, may be related to Cushing’s syndrome or the associated obesity.
Results
The operative mortality for adrenalectomy in patients with Cushing’s syndrome has been reported to be 2% to 6%, and the occurrence of Nelson’s syndrome (the development of invasive pituitary tumors after adrenalectomy) seems minimal. Most patients with pituitary Cushing’s syndrome who have poor results from pituitary surgery are cured with bilateral adrenalectomy, and a successful outcome should occur after adenalectomy in the patient with adrenal hyperplasia or an adrenal adenoma correctly diagnosed.
In the small number of patients with adrenal malignancy, sugery may be curative if the tumor is localized, but metastatic disease responds poorly to the combination of adrenalectomy, radiation, and chemotherapy. It still remains, however, that management of these complicated endocrinologic patients is a continuing challenge for the urologic surgeon.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: