CORTICOTROPIN-SECRETING PITUITARY TUMOR
Corticotropin (adrenocorticotropic hormone [ACTH])-secreting pituitary adenomas stimulate excess adrenal secretion of cortisol, resulting in the signs and symptoms characteristic of Cushing syndrome (see Plate 3-9). ACTH-secreting pituitary tumors are typically benign microadenomas (10 mm in largest diameter); occasionally, they are macroadenomas, and very rarely they are carcinomas. Treatment of choice for an ACTH-secreting pituitary adenoma is transsphenoidal selective adenectomy. Surgical success is defined as cure of Cushing syndrome and intact anterior and posterior pituitary function.
The most common operative approach
is an endonasal approach (with use of an endoscope), traversing the sphenoid
sinus (transsphenoidal) and through the floor of the sella (see Plate 1-31).
Corticotroph adenomas are basophilic and stain positively for ACTH on immuno-histochemistry. Tissue adjacent to the adenoma usually shows Crooke hyaline
change, a result of atrophy of normal corticotrophs. Cure rates are 80% to 90%
when a microadenoma can be localized preoperatively with either magnetic
resonance imaging (MRI) or inferior petrosal sinus sampling (see Plate 3-10). A
lack of cure in patients with microadenomas is attributable to either their
small size, so they cannot be seen at surgery, or to an inaccessible location
(e.g., cavernous sinus). MRI should be performed with a high-strength magnet
(e.g., 3 tesla) and gadolinium enhancement. Only about half of ACTH-secreting
pituitary tumors are large enough to be detected by MRI. In addition,
approximately 10% of healthy individuals have an apparent microadenoma on MRI;
thus, in a patient with Cushing syndrome, an apparent small sellar adenoma on
MRI is not specific for a corticotroph adenoma. The lower cure rate (60%) for
macroadenomas is usually because of cavernous sinus involvement that prevents
complete resection.
On the day of surgery, these
patients should receive an intravenous dose of glucocorticoid (e.g.,
hydrocortisone, 100 mg). The serum cortisol concentration should be measured
the morning after surgery (before additional exogenous glucocorticoid
administration) to document a short-term cure, defined as a low serum cortisol
concentration (e.g., 1.8 g/dL). If the patient develops symptoms of acute
glucocorticoid withdrawal before the serum cortisol laboratory result is
available, stress dosages of glucocorticoids should be administered (e.g.,
hydrocortisone, 100 mg intravenously twice daily). The glucocorticoid dosage is
then decreased daily, and patients are typically discharged from the hospital
on dosages of exogenous orally administered glucocorticoids twofold above the
standard replacement therapy dosage (e.g., prednisone, 10 mg in the morning and
5 mg at 4 pm daily). However, this dosage should be adjusted according to the
severity of hypercortisolism preoperatively to prevent severe steroid
withdrawal symptoms. Then the dosage of exogenous glucocorticoid is slowly
tapered to a standard replacement dosage over 4 to 6 weeks after operation. The
hypothalamic corticotropin-releasing hormone neurons and the atrophic anterior
pituitary corticotrophs take months to recover from chronic suppression. Most
patients tolerate a single dose of a short-acting glucocorticoid (e.g., 15-20
mg of hydrocortisone every morning) starting 8 to 12 weeks after surgical cure.
The 8 am ld be measured
every 6 weeks; venipuncture should
be performed before taking a morning dose of hydrocortisone. The serum cortisol
concentration will slowly increase from undetectable levels to a concentration
higher than 10 g/dL; when this occurs, the hydrocortisone dosage can be
tapered and discontinued over 2 weeks. With this postoperative management protocol,
the patient with typical pituitary-dependent Cushing syndrome requires
exogenous administration of glucocorticoids for approximately 12 months after
curative pituitary surgery. The signs and symptoms related to Cushing syndrome
resolve very slowly over the first 6 months after surgery.
However, even when the postoperative
serum cortisol concentration is low, a risk for recurrent disease remains if a
small number of viable adenomatous corticotroph cells are not resected at
surgery, they multiply over time and eventually have
the ACTH secretory mass to cause recurrent Cushing syndrome. The average time
to clinically evident recurrence is 3 to 4 years. Thus, all patients should be
followed up annually and assessed for recurrent disease.
Patients with Cushing syndrome are
at increased thromboembolic risk perioperatively, and prophylactic measures to
prevent deep venous thrombosis (including starting ambulation the day after
surgery) are encouraged.
When transsphenoidal surgery fails
to cure a patient with pituitary-dependent Cushing syndrome, the two main
treatment options are to perform another transsphenoidal surgery or to perform
bilateral laparoscopic adrenalectomy. Less frequently used options are
radiation therapy to the sella or pharmacotherapy to decrease adrenal cortisol production.
