generally better than those results reported from tumor registries.

Cushing Disease

Surgical results for Cushing disease are summarized in Table 78-8. Remission rates for microadenomas

are generally from 70% to 90%. In those patients not in remission after the initial procedure, a second

exploration is sometimes recommended, which can achieve remission in an additional 50% to 70% of

patients.46,47 While early as opposed to late reoperation is technically less challenging, delayed

remissions have been reported, and it is important to determine that postoperative levels have

plateaued at an elevated level before proceeding with reexploration.48

Table 78-7 Recent Surgical Results for Acromegaly

Table 78-8 Recent Surgical Results for Cushing Disease

MANAGEMENT OF PITUITARY ADENOMAS BY SYNDROME

With the advent of medical therapy for some of the secretory tumors, surgical indications have changed,

and surgical decision making needs to be considered in the context of the available treatment options.

Prolactinomas

8 Medical treatment with dopamine agonists (DAs) is considered first-line therapy for most patients

with prolactinomas even those with large and invasive tumors.54 Not all patients require treatment –

patients with asymptomatic, stable microadenomas, who are not pursuing fertility, can often be

followed expectantly. The commonly used agents – bromocriptine and cabergoline – are both oral

agents with excellent efficacy, minimal side effects (usually GI disturbances, although cognitive issues

and psychological effects have been reported, including depression, anxiety, and impulsivity), and are

relatively inexpensive. Cabergoline is more effective and generally better tolerated than bromocriptine.

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High doses of cabergoline (>3 mg/d) have been associated with cardiac valvular dysfunction, but this

does not appear to be a significant risk in the dose range usually prescribed for prolactinomas (typically

0.5–2.0 mg/wk, Table 78-9). Because they act as metabolic inhibitors and are not cytotoxic, lifelong

therapy is usually required, although there are some reports of apparently long-term remission after

discontinuation of the drugs.55 The tumor shrinkage in response to these agents is often dramatic.

Surgical treatment is indicated after the failure of medical therapy, intolerance to the medications, and

in cases where the patient prefers the possibility of surgical remission to life-long medical treatment.

Other indications for surgery include cerebrospinal fluid leak, occurring as a result of shrinkage of

large, invasive prolactinomas in response to medical therapy, and pituitary apoplexy, which may rarely

complicate use of dopamine agonists. Relative indications include cystic tumors, which may not shrink

with medical treatment, and in infertile women who wish to become pregnant without medication.

Long-standing visual dysfunction will often improve after tumor shrinkage from medical treatment,

while rapidly progressive visual loss, especially associated with hemorrhage, mandates surgical

removal. Radiation therapy can be recommended for tumors unresponsive to medical and surgical

treatment. Temozolomide, an orally active alkylating agent, has been administered (“off label”) to some

patients with aggressive pituitary adenomas or carcinomas (including, but not limited to, aggressive or

malignant prolactinomas), and may transiently achieve tumor control.

Acromegaly

9 Surgery remains first-line treatment in most cases, though some would argue for primary medical

treatment in those cases unlikely to be surgically cured, or in patients who are not optimal surgical

candidates.56 The available medical treatments include somatostatin analogs (SSAs), dopamine agonists,

and growth hormone receptor antagonists. Each treatment modality has its own relative advantages and

disadvantages. Surgery is rapidly effective in lowering GH levels, leads to immediate relief of symptoms

from mass effect (visual loss), and has the potential to be curative, depending upon the size and degree

of tumor invasiveness. Cabergoline, the most potent dopamine agonist, is sometimes effective in

acromegaly (leading to endocrine remission in 20% to 30% of cases), but usually only when the IGF1

level is minimally elevated (Table 78-10). However, it is an oral agent with minimal risk and relatively

inexpensive. Its use in acromegaly is not FDA approved. The SSAs – octreotide and lanreotide – are

effective in normalizing IGF1 in about 40% to 50% of patients previously selected for responsiveness to

SSAs, though recent studies in unselected de novo patients report effectiveness in only 20% to 25%.

They lead to tumor shrinkage to some degree also in about 40% to 50% of cases, though the shrinkage

seen is usually not dramatic (unlike the shrinkage seen in prolactinomas with DAs). They are both

injectable agents, given every 4 weeks in their long-acting forms, and usually well tolerated; the most

common side effects are GI disturbances and occasionally cholelithiasis and hyperglycemia. Both agents

are expensive. A recent study compared the use of octreotide and pasireotide in acromegaly; in de novo

patients (no previous surgery) remission was achieved in 26% with pasireotide and 17% with

octreotide.57 The growth hormone receptor pegvisomant blocks the peripheral action of growth

hormone and leads to dramatic lowering of the IGF1 level in up to 95% of patients, but has no direct

antitumoral effect. Because of this, it is best used in combination with the SSAs in cases of incomplete

response, or to control the IGF1 while awaiting the beneficial effects of radiation treatment. Arguments

have been made for both pretreatment of surgical cases with SSAs, and debulking of unresectable

tumors prior to medical therapy. In three randomized studies, pretreatment was shown to improve

postoperative remission rates, but the control remission rate in these studies was lower than would be

expected from comparisons to the literature. In a recent meta-analysis, a borderline positive affect with

pretreatment was detected in 10 studies, both randomized and retrospective, which did not reach

statistical significance, while the analysis of the prospective controlled trials (with historically low

pretreatment remission rates) was statistically significant in showing benefit.58 Pretreatment in

symptomatic acromegalic patients can, however, improve anesthetic risk by improving attendant

comorbidities, especially cardiomyopathy and airway management, and for this reason alone is

sometimes worthy of consideration.59 The indications for debulking an unresectable tumor have been

debated; since SSA treatment appears to be more effective with lower IGF1 levels,60 an argument can be

made for removing as much tumor as possible and treating the remainder with medication. In cases

where primary medical treatment was unsuccessful, surgical debulking has been shown to improve

remission, even if surgical “cure” cannot be achieved.61 Radiation therapy is usually a third-line option

for patients who are not in remission after surgery and do not respond or tolerate medical therapy. A

flowchart for the management of acromegaly is shown in Algorithm 78-1.

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