Table 78-9 Medications Used to Treat Prolactin-Secreting Pituitary Adenomas

Table 78-10 Medications Used to Treat Acromegaly

Algorithm 78-1. Treatment algorithm for acromegaly.

Table 78-11 Medications Used to Treat Cushing Disease

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Cushing Disease

Surgical excision is generally considered to be first-line treatment; if unsuccessful, early reexploration

has been recommended with some additional degree of success.46 Surgical remission leads to immediate

lowering of ACTH levels and cortisol production, and steroid replacement is required as the normal

gland will remain suppressed for months. If transsphenoidal surgery is unsuccessful, a number of

treatment options are available. Medical therapy can control hypercortisolemia by inhibition of cortisol

production by the adrenal glands (ketoconazole,62 metyrapone, mitotane, etomidate), at the level of the

pituitary tumor by acting on somatostatin receptors (pasireotide)63 or dopamine receptors

(cabergoline),64 or by cortisol receptor blockade (mifepristone),65 and combination therapy has been

suggested as well.66 Medications are most commonly used in patients who have persistent

hypercortisolism after pituitary surgery and are not candidates for additional surgery. Each medication

has its attendant set of side effects, including liver function abnormalities with ketoconazole,

hyperglycemia with pasireotide, GI disturbances with high-dose cabergoline, and hypokalemia and

endometrial thickening with mifepristone; none represents optimal therapy but each may offer

advantages in the individual patient (Table 78-11). Only pasireotide and mifepristone are FDA approved

for use in patients with Cushing disease. Bilateral adrenalectomy remains a viable option, with

immediate resolution of hypercortisolemia, but requires lifelong mineralocorticoid and glucocorticoid

replacement. It is associated with radiographic progression of the pituitary adenoma in about half the

cases, and a smaller number of patients may develop Nelson syndrome.67 Radiosurgery with interim

medical control is often a reasonable option after unsuccessful surgery; normalization of cortisol levels

occurs in about 50% to 70% of patients within 2 years of treatment, but with a significant risk of

anterior hypopituitarism.68,69 A flowchart for the management of Cushing disease is shown in Algorithm

78-2. Recurrent Cushing disease after initially successful surgery remains a significant problem.

Reported recurrence rates are approximately 2% per year,29 but some series report an overall incidence

of as high as 25%.70 Reexploration for recurrence is a reasonable option with success rates on the order

of 50%; but the alternative therapies described above merit consideration as well.71,72

Nonfunctioning Tumors

Surgical removal remains as first-line treatment; there are no good medical options (as the response to

dopamine agonists or SSAs has been poor). Small nonfunctioning tumors (<1 cm) can be followed with

serial imaging, but macroadenomas should usually be resected, especially those which are close to the

chiasm or enlarging on serial scans, even without visual abnormalities. After subtotal resection it is in

many cases reasonable to follow the residual tumor, with reoperation or radiation therapy reserved for

those which later enlarge. Guidelines for the management of pituitary incidentalomas have been

recently published.73

Thyrotropin-Secreting Pituitary Adenomas

2225

Pituitary surgery is first-line therapy in most cases. Patients with hyperthyroidism can be pretreated

with SSAs or methimazole in order to control hyperthyroidism preoperatively, if present. After surgery,

patients with residual tumors or persistent hyperthyroidism may benefit from SSA therapy, which is

very effective in controlling hyperthyroidism and also affords some degree of tumor control. Radiation

therapy is an alternative option in patients who are not in remission after pituitary surgery.

SOCIOECONOMIC CONSIDERATIONS

10 A number of socioeconomic considerations now affect the practice of pituitary surgery. The volumeoutcome relationship, which has been shown to be manifest in a number of surgical subspecialties, holds

true here as well. This was originally suggested by a study showing improved outcomes for acromegaly

with a dedicated pituitary surgeon.74 Further studies have demonstrated a decrease in complication rate

with increased experience,75 and a significant decrease in operative mortality after pituitary surgery in

high-volume as opposed to low-volume centers.76 With the multiplicity of available treatment

modalities, comparative cost–benefit analyses are now being performed. Treatment algorithms in

acromegaly which incorporated transsphenoidal surgery were shown to be less expensive than those

using medical therapy alone, and algorithms using primary surgery followed by adjunctive medical

treatment as opposed to the converse approach were shown to be 30% less costly overall.77 In Cushing

disease, the economic burden of managing patient comorbidities was shown to significantly decrease

after successful surgery.78 Despite the introduction of new pharmacologic agents, it is likely that

surgery will continue to play a major role in the treatment of pituitary disorders; given the multiplicity

of options, however, care is best individualized for a given patient in a multidisciplinary setting.

Algorithm 78-2. Treatment algorithm for Cushing disease.

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