Surgery may be followed by a decrease, increase, or no changes in hormonal secretion by the nonadenomatous pituitary cells. The variable response was illustrated in a study of 56 patients with nonsecreting tumors: three with normal pituitary function preoperatively had postoperative deficiencies; 24 with preoperative hormonal deficiencies had additional postoperative deficiencies; and 29 with preoperative deficiencies had recovery from a deficiency.

The risk of complications is inversely proportional to the experience of the surgeon in performing transsphenoidal surgery. In one study, 958 neurosurgeons reported their own experiences in response to a questionnaire Both serious complications, such as loss of vision and death, and less serious complications, such as hormonal deficiencies, were higher among surgeons who had performed fewer transsphenoidal procedures For example, among neurosurgeons who reported performing fewer than 200 transsphenoidal procedures, 1.2 percent of procedures resulted in death, but among neurosurgeons who reported performing more than 500 procedures, only 0.2 percent resulted in death. A second study utilized a national database and found that among 825 surgeons who performed 5497 operations, the complication rate was also less among surgeons who performed more transsphenoidal procedures.

Preoperative management — The most important aspects of the preoperative preparation for surgery include:

   Identifying the sellar lesion as a gonadotroph adenoma, which must be distinguished from a nonpituitary lesion in or near the sella, which might best be approached transcranially.

   Identifying a marker, such as a high serum follicle-stimulating hormone (FSH) or free alpha subunit concentration, which can be used to monitor the response to surgery and subsequent therapy.

   Identifying an experienced pituitary surgeon.

   Ensuring that the patient is hormonally stable. It is therefore important to determine if the patient has hypothyroidism, which increases the risk of respiratory arrest following postoperative administration of opiates or barbiturates. Hypothyroidism should be corrected preoperatively or these agents should be used in lower than usual doses.

Postoperative management can be considered in terms of the immediate, the short-term, and the long-term.

Immediate postoperative management — In the few days after surgery, the patient may develop diabetes insipidus, SIADH, or both. In one series of 92 patients, 25 percent became hyponatremic within one week of surgery; another 20 percent had at least transient diabetes insipidus. Both abnormalities were associated with increased manipulation of the pituitary and its stalk during surgery. Although relative cortisol deficiency may contribute to the hyponatremia, the major cause is inappropriate ADH release from the injured posterior pituitary gland. The fall in the plasma sodium concentration is most severe on the sixth to seventh postoperative day

Thus, both urine output and serum sodium concentrations should be measured often. Patients with polyuria due to diabetes insipidus should be treated with aqueous vasopressin, either as subcutaneous bolus doses or as a continuous intravenous infusion.  Desmopressin (dDAVP), which is longer-acting, should be avoided at this time, because it might cause hyponatremia if the diabetes insipidus suddenly remits, particularly if it is then followed by the SIADH.

dDAVP should be used if diabetes insipidus lasts for more than four to five days or is present at the time of discharge from the hospital. Maintenance hydrocortisone replacement should also be prescribed at discharge.

Short-term postoperative management — Four to six weeks after discharge from the hospital, the patient should be evaluated for the amount of residual adenoma, visual function (by acuity and visual fields), and hormonal function of the nonadenomatous pituitary. A crude estimation of the amount of residual adenoma can be determined by magnetic resonance imaging, but artifacts of surgery may obscure the actual amount of residual adenoma tissue for several months. A more accurate estimate of the amount of residual adenoma at this time can be attained by monitoring the serum concentration of any gonadotroph adenoma product, such as FSH or the free alpha subunit, that had been elevated before surgery.

Hormonal function of the nonadenomatous pituitary should be evaluated regardless of whether it was normal or abnormal prior to surgery. This evaluation should include measurements of:

Radiation therapy is usually not employed as primary therapy for gonadotroph and other clinically nonfunctioning pituitary adenomas, because its effects occur too slowly to be appropriate when a patient has visual impairment. However, it could be used as primary therapy in selected patients whose adenomas are sufficiently large to threaten the optic chiasm but are not causing visual impairment or other neurologic symptoms.

Conventional radiation therapy — Conventional therapy is supervoltage radiation, administered in 23 to 25 daily doses of 2 Gy each. Side effects can occur both during therapy and up to 10 years later.

In a report of fractionated stereotactic radiotherapy (FSRT) in 68 patients, 65 of whom had initially undergone transsphenoidal surgery and had either residual (n = 54) or recurrent tumor (n = 11), the following results were seen after observation for a median of 30 months:

   Tumor size decreased in 26 patients, remained stable in 41, and increased in one patient.
   Visual fields improved in 28 patients, were stable in 24, and worsened in 2 patients in those who had visual field testing.
   Hypopituitarism developed in four patients.
   Optic neuropathy, attributable to the radiation, occurred in two patients.

These results on adenoma size seem good, although the period of observation was relatively short compared with the natural history of pituitary adenomas and to periods of observation reported for conventional radiation therapy. The occurrence of two cases of optic neuropathy is troubling, however, and suggests that the goal of reducing neurologic complications by this stereotactic approach will not be realized.

Two reports describe the results of single dose radiotherapy in patients who had residual or recurrent adenomas following transsphenoidal surgery. In one report, 33 patients were treated with doses of 12 to 20 Gy from a linear accelerator and followed for a median of 43 months. In the other, 45 patients were treated with 11 to 20 Gy of gamma radiation from a cobalt source, and 30 were evaluated during a median observation period of 55 months. The results were similar in the two studies:

   Actuarial tumor control rates were >95 percent.
   No neurologic complications occurred.
   Actuarial rates of developing new anterior pituitary hormone deficiencies were 14 to 41 percent at 5 to 6 years.

Stereotactic radiotherapy has also been utilized for other pituitary tumors

Dopamine agonists — Although dopamine does not decrease gonadotropin secretion to an appreciable degree in normal subjects, bromocriptine has been reported to reduce the secretion of intact gonadotropins and the free alpha subunit in a few patients and even to improve vision in one patient; however, it has not been shown to reduce adenoma size

Octreotide — The cell membranes of some clinically nonfunctioning pituitary adenomas have somatostatin receptors. Two groups have administered octreotide (a somatostatin analogue) to such patients. One found improvement in visual fields in three of four patients, but no decrease in adenoma size The other found decreases in serum alpha subunit values in three of six patients and a reduction in tumor size and visual impairment in two each; there was, however, no correlation among the three measurements

GnRH superactive agonist analogs — The rationale for the use of gonadotropin-releasing hormone agonists in patients with gonadotroph adenomas is that chronic administration causes down-regulation of GnRH receptors on, and decreased secretion of gonadotropins from normal gonadotroph cells. . Unfortunately, administration of GnRH agonist analogs to patients with gonadotroph adenomas usually has either an agonist effect or no change in gonadotropin secretion and does not effect on adenoma size

GnRH antagonist — Administration of a GnRH antagonist is the most effective approach tested thus far in suppressing FSH secretion by gonadotroph adenomas. In one report, for example, administration of Nal-Glu GnRH for one week to men with gonadotroph adenomas normalized their high serum FSH concentrations  In another study serum FSH concentrations remained low for the entire six-month treatment period; however, adenoma size did not decrease. These results suggest that FSH secretion by gonadotroph adenomas, but not adenoma size, is dependent upon endogenous GnRH.

NO TREATMENT — Gonadotroph adenomas that are asymptomatic and not an immediate threat to vision may not require treatment, especially if the patient is elderly or infirm. This situation is increasingly common, because an increasing number of gonadotroph or nonfunctioning adenomas are detected as incidental findings when MRI is performed for other reasons, such as head trauma. Hormonal deficiencies should still be replaced, and reevaluation of adenoma size and function of the nonadenomatous pituitary should be performed at yearly intervals.