Assessment of long-term remission of acromegaly following surgery

OBJECT: The criteria for remission of acromegaly following transsphenoidal adenoma resection are in evolution. In the present study the authors evaluate the utility of predicting long-term remission by reference to a single fasting growth hormone (GH) level on the 1st postoperative day. METHODS: A retrospective analysis was conducted on 181 patients with acromegaly who underwent transsphenoidal resection between 1973 and 1990 and completed a 5-year follow-up period. Fasting serum GH levels were obtained in all patients on the 1st postoperative day in the absence of exogenous glucocorticoids. All patients participated in a follow-up evaluation lasting at least 5 years, which included measurements of serum insulin-like growth factor-I (IGF-I) levels as an index of acromegalic activity. Among the 181 patients, GH levels ranged from 0 to 8 ng/ml in 131 (72%) on the 1st postoperative day, suggesting biochemical remission. This group included 107 (84%) of the 127 patients with microadenomas, but only 24 (44%) of the 54 with macroadenomas. Nevertheless, 15 (11%) of the 131 patients who initially had attenuated GH levels displayed recurrent acromegaly within the first 2 years (with elevated levels of IGF-I in all cases, and abnormalities appearing on magnetic resonance images in nine cases). Only one of 116 patients in whom the initial postoperative GH level was lower than 2 ng/ml experienced a recurrence, whereas 14 (93%) of the 15 patients with postoperative GH levels between 2.2 and 8 ng/ml subsequently displayed biochemical evidence of acromegaly. CONCLUSIONS: The findings indicate that a fasting morning serum GH level lower than 2 ng/ml on the 1st postoperative day portends long-term biochemical remission of acromegaly, whereas higher levels are a significant marker for recurrent disease.     

Changing patterns of insulin-like growth factor-I and glucose-suppressed growth hormone levels after pituitary surgery in patients with acromegaly

OBJECT: According to a recent consensus statement on the treatment of acromegaly, its biochemical cure is defined as the normalization of age- and sex-adjusted insulin-like growth factor (IGF)-I levels and the suppression of growth hormone (GH) by glucose to lower than 1 ng/ml. The present study was prompted by the clinical observation that many cases of acromegaly can be considered cured according to one criterion but not others at different moments in a patient's postoperative course. METHODS: Fifty-three patients with acromegaly (30 women and 23 men) harboring nine microadenomas and 44 macroadenomas were evaluated after surgery by assessing age- and sex-adjusted IGF-I levels as well as glucose-suppressed GH levels. Fifty of these patients were studied more than once during follow up. Acromegaly was categorized as cured if the patient's IGF-I level was normal and their glucose-suppressed GH level was lower than 1 ng/ml; the disease was considered to be active if the patient's IGF-I level was high and the GH nadir was higher than 1 ng/ml following administration of glucose. Discordant categories of the disease were found in patients with high IGF-I levels and a GH nadir lower than 1 ng/ml after glucose administration and in those with normal IGF-I levels and a GH nadir higher than 1 ng/ml after glucose intake. At the first postoperative biochemical evaluation (1-3 months), 34% of patients harboring macroadenomas were classified as having been cured of acromegaly, 39% as having the active disease, and 27% as having the discordant form of the disease. When last evaluated (> or = 12 months postoperatively), the percentage of patients with the discordant form dropped to 14% and the proportion of cases cured and active was 44% and 41%, respectively. Of the nine patients with microadenomas, 44.4% were cured of acromegaly, 33.2% had the active disease, and 22% had the discordant variety on first evaluation. Twelve months or longer after transsphenoidal surgery, 55.5% of cases were cured, 11.1% were active, and 33% were discordant. In most cases, the discordant variety developed because of a persistently elevated level of IGF-I, followed by an incompletely suppressed GH level. Nineteen patients (38%) modified their biochemical category. In 15 of these patients this change in category was due to a change in IGF-I levels, becoming normal in 12 patients and rising to above normal range in three. A tumor remnant was demonstrated on magnetic resonance images in only four of these 19 patients. CONCLUSIONS: The authors conclude that the discordance rate between the biochemical markers that define cure in acromegaly is higher than previously reported, and the biochemical status assigned to a patient early in the postoperative course is very likely to change later, particularly when initially discordant.     

Pregnancy following transsphenoidal resection of prolactin-secreting pituitary tumors

This report describes 200 women in the childbearing age group with prolactin-secreting pituitary adenomas treated by transsphenoidal microsurgery. There were 136 patients with microadenomas (10 mm or less in diameter), 30 with macroadenomas, 11 with invasive adenomas, and one with hyperplasia. The overall rate for postoperative normalization of serum prolactin was 57%, and it was 72% for those patients with microadenomas. Pregnancy was desired by 90 women, and 78 (84%) became pregnant, although 10 required postoperative bromocriptine to do so. Serious postoperative complications were rare, and produced no major morbidity. The results of surgery were most favorable in women with microadenomas and preoperative serum prolactin levels of 100 ng/ml or less.     

Transsphenoidal surgery for Cushing's disease: endocrinological follow-up monitoring of 82 patients

OBJECTIVE: Transsphenoidal surgery is the preferred treatment modality for adrenocorticotropic hormone-secreting pituitary adenomas. In the past 2 decades, several institutions in the United States and Europe have reported remission rates of 70 to 85% after transsphenoidal surgery for treatment of Cushing's disease. We analyzed our postoperative results for a large cohort of patients with Cushing's disease. METHODS: Eighty-two patients with adrenocorticotropic hormone-secreting adenomas (79 microadenomas and 3 macroadenomas) underwent transsphenoidal surgery between 1990 and 2000. Seventy-seven patients were surgically treated for the first time, and 13 patients underwent reoperations (5 had undergone the first operation elsewhere) because of previous surgical failure (10 patients) or recurrence (3 patients). The mean postoperative follow-up period was 4.2 +/- 2.8 years. Biochemical remission was defined as postoperative normalization of elevated 24-hour urinary free cortisol secretion and suppression of morning cortisol levels with 1 mg of dexamethasone. RESULTS: Remission was achieved for 78% of all patients after one operation and for 62% of patients who underwent a second operation. The recurrence rate was 5%. Ten patients did not exhibit a visible tumor on magnetic resonance imaging scans, and the other patients were divided according to adenoma size (2-5 or 6-10 mm). Remission rates were similar for the three groups of patients (78-80%). Pituitary tumor stained for adrenocorticotropic hormone was detected in 78% of resected pituitary tissue specimens obtained from patients who achieved remission, compared with 53% from patients who experienced surgical failure (P = 0.06). CONCLUSION: Our series demonstrates the efficacy of transsphenoidal surgery for Cushing's disease resulting from pituitary microadenomas. Microadenoma size had no effect on the remission rate. Reoperations are indicated after initial surgical failures.     

Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery

OBJECT: Prolactin-secreting pituitary adenomas may be managed by surgery, medication, radiotherapy, or observation. The authors reviewed a consecutive series of patients who were followed for at least 5 years after surgery to assess the prognostic significance of preoperative factors (tumor size and prolactin level) and an immediate postoperative factor (prolactin level obtained the morning after surgery) on long-term hormonal outcome, thereby clarifying the indications for surgical removal of tumor, the definition of successful treatment outcomes, and the nature of "recurrent" tumors. METHODS: Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (< or = 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome. CONCLUSIONS: Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure.     

Factors Associated with Biochemical Remission after Microscopic Transsphenoidal Surgery for Acromegaly

Objectives To analyze surgical outcomes and predictive factors of disease remission in acromegaly patients who underwent microscopic transsphenoidal surgery (TSS) for a growth hormone (GH)-secreting adenoma. Design A 6-year retrospective review of 86 consecutive acromegaly surgeries. Setting Procedures performed at a single institution by a single surgeon. Participants Seventy acromegaly patients. Main Outcome Measures Demographic information, preoperative laboratory values, tumor imaging data, and morphological and immunohistochemical data were collected. Predictive values using the latest and most stringent biochemical remission criteria were determined using univariate and multivariate statistical analyses. Results Remission rate for 59 (18 males) acromegaly patients meeting the study inclusion criteria was 52.5%. Remission rates for micro- and macroadenomas were 81.8% and 45.8%, respectively. Patients of older age, with a smaller tumor, lower Knosp grade, lower preoperative GH, and insulinlike growth factor 1 levels were more likely to achieve remission. Remission rate decreased significantly with repeat surgeries. Those patients with adenomas that stained positive for somatostatin receptor subtype 2A were less likely to experience tumor recurrence and more likely to respond to medical treatment with persistent or elevated GH hypersecretion. Conclusions Microscopic TSS continues to be a viable means for treating acromegaly patients. Patients should be followed long term.     

Radiosurgery of growth hormone-producing pituitary adenomas: factors associated with biochemical remission

OBJECT: The authors reviewed outcomes after stereotactic radiosurgery for patients with acromegaly and analyzed factors associated with biochemical remission. METHODS: Retrospective analysis was performed for 46 consecutive cases of growth hormone (GH)-producing pituitary adenomas treated by radiosurgery between 1991 and 2004. Biochemical remission was defined as a fasting GH less than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor-I (IGF-I) level while patients were not receiving any pituitary suppressive medications. The median follow up after radiosurgery was 63 months (range 22-168 months). Twenty-three patients (50%) had biochemical remission documented at a median of 36 months (range 6-63 months) after one radiosurgical procedure. The actuarial rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and 60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.2-6.9, p = 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (HR 4.2, 95% CI 1.4-13.2, p = 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years. CONCLUSIONS: Discontinuation of pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for patients with acromegaly. Patients with GH-producing pituitary adenomas should not undergo further radiation therapy or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.     

Functional treatment of acromegaly by transsphenoidal microsurgery

The authors have analyzed the results from 41 acromegalic patients who underwent transsphenoidal surgery. In 31 patients, postoperative growth hormone (GH) levels fell and remained below 10 ng/ml. This represents an endocrinological "cure" of 78%. In the remaining 10 cases, postoperative GH values have not stabilized below 10 ng/ml, although seven show some clinical improvement. The results were particularly good in those cases of localized adenomas, which allowed a selective removal while maintaining pituitary function within normal limits in 65.5% of cases. The postoperative GH level in this group fell and remained below 10 ng/ml in more than 90% of cases. Four patients required reoperation to normalize the GH levels which had not been sufficiently modified after the first operation; only one of them remained with plasma GH levels above normal limits. There were no deaths in this series. Rhinorrhea occurred as a postsurgical complication in four cases. In three this disappeared with bed rest and lumbar drainage; in the other, surgical repair was necessary. The occurrence of surgical complications has decreased as our experience has increased, and the need for reoperation has been unusual after the first year of our study.     

Cushing's disease and corticotrophic adenoma: results of pituitary microsurgery

Between November 1994 and June 2001, 194 patients with Cushing's disease underwent transsphenoidal surgery: 167 patients had adenomectomy, 14 had ante hypophysectomy, 5 had subtotal hypophysectomy, 4 had hemihypophysectomy 4 had central hypophysectomy. Complications occurred in 18 patients (9.3%), including 4 deaths (three were apparently not related to surgery). Remission of disease was achieved in 162 of 190 (85.3%) patients analyzed. Surgical failures were associated with lack of pituitary adenoma, size of the tumor and invasiveness. Among patients with confirmed adenomas, the rate of remission was significantly higher (p<0.01) in patients with microadenomas (92.6%) than in patients with macroadenomas (66.7%). Reoperation in 6 failures was followed by remission in 4 cases. The overall remission rate was 87.4%. In the 162 patients with immediate success, duration of follow-up was 10.0 +/- 5.9 years (m +/- DS; median=10.0). Recurrence of the disease occurred in 24 (14.8%) of 162 patients at a mean 4.8 years (range: 0.8-12.0 years). Our longest sustained remission is 25.6 years. Actuarial analysis indicates that the probability of a patient remaining well 12 years after surgery is 80.0%. It is 86.2% in microadenomas versus 52.5% in macroadenomas and 94.5% in the patients with postoperative hypocortisolism versus 59.2% in the others.     

Results of transsphenoidal microsurgery for growth hormone-secreting pituitary adenoma in a series of 214 patients

Of 214 patients with acromegaly who underwent transsphenoidal microsurgical resection of a pituitary adenoma, 54% had growth hormone (GH) levels below 5 ng/ml and 74% had levels less than 10 ng/ml immediately after surgery. Among the 174 patients who could be contacted for long-term follow-up review (average duration 76 months), most recent GH determinations were available for 165. Of these 165 patients, 131 (79.4%) have a GH level less than 5 ng/ml and 153 (92.7%) have a level below 10 ng/ml; these represent 75.3% and 87.9%, respectively, of the total 174 patients reviewed. Fifty-two patients received postoperative radiation therapy. Nine patients underwent reoperation. There were five cases of tumor recurrence following an apparent surgical cure (4.3%), nine new instances of anterior pituitary hypofunction (5%), and five failures of multimodality therapy (2.3%). There were no perioperative deaths, five cases of cerebrospinal fluid leak requiring surgical repair (2.2%), and four cases of postoperative meningitis (1.8%). Permanent diabetes insipidus did not occur. Two of 52 patients who were irradiated postoperatively had severe complications; 23 (54.8%) of 42 patients who were available for follow-up evaluation had developed panhypopituitarism; and eight (19%) of 42 had normal pituitary function an average of 44 months postirradiation.     

Evaluation of selective transsphenoidal adenomectomy by endocrinological testing and somatomedin-C measurement in acromegaly

A series of 29 previously untreated patients with acromegaly underwent transsphenoidal adenomectomy. Pre- and postoperative evaluation consisted of measuring growth hormone (GH) secretory dynamics during an oral glucose tolerance test (OGTT), the insulin hypoglycemia test, and the thyrotropin- and gonadotropin-releasing hormone (TRH/GnRH) test, and by obtaining the basal somatomedin-C level. After surgery, clinical and biochemical amelioration was achieved in all but two patients. In the whole group, basal GH and somatomedin-C levels decreased from a mean (+/- standard error of the mean) of 52.3 +/- 12.7 to 11.1 +/- 6.3 ng/ml and from 7.6 +/- 0.7 to 2.5 +/- 0.5 U/ml, respectively. Application of different criteria of cure revealed that 19 patients (66%) had basal GH levels below 5 ng/ml, 17 patients (59%) had normal somatomedin-C values, 16 patients (55%) had complete GH suppression (less than 1 ng/ml) during OGTT, and 13 patients (45%) met the above-mentioned criteria with disappearance of the paradoxical GH response to TRH/GnRH test. Evaluation of GH secretion by insulin hypoglycemia testing was useless in assessing the outcome after neurosurgery. When only patients with a normal somatomedin-C level and complete GH suppressibility during OGTT were considered "cured," the main favorable prognostic factor was intrasellar tumor localization, since 15 (75%) of 20 patients were "cured," as opposed to only one (11%) of nine with extrasellar extension of the adenoma. During the follow-up period, no tumor recurrence was detected in any of the "cured" patients. In these subjects somatomedin-C levels remained stable in all except two patients, who showed a slow increase within the normal range of somatomedin-C concentration. These data confirm that transsphenoidal surgery is the most effective form of treatment in previously untreated acromegalic patients and that normalization of somatomedin-C levels reflects normal GH secretion. Measurement of somatomedin-C could replace more extensive endocrinological testing during monitoring of treated acromegalic patients.     

Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays

Background

Early detection of residual disease may benefit management strategies in patients undergoing transsphenoidal surgery for acromegaly. This requires establishing objective thresholds for early postoperative growth hormone (GH) assays, and incorporating these parameters into a scale for outcome prediction.

Method

We analyzed a database containing the records of 86 patients who had undergone gross total transsphenoidal resection of GH-secreting pituitary adenomas. Early postoperative biochemical testing included a morning fasting basal GH assay on the first postoperative day (POD1) and a second GH assay following suppression with 100 g of oral glucose on the seventh postoperative day (POD7). Remission was defined as a normal IGF-1 with either a GH nadir <0.4 ng/ml following suppression with oral glucose or a basal fasting GH <1 ng/ml on follow-up dated >3 months after surgery. Receiver operator characteristic (ROC) curves identified optimal thresholds for all biochemical parameters. Logistic regression analysis assessed the statistical significance of factors associated with cure. A point system was developed, employing regression coefficients obtained from the multivariate statistical model to quantify the impact of each predictor on cure.

Results

Remission was achieved in 34.6 % of patients and was associated with smaller, non-invasive tumors with lower preoperative, POD1 and POD7 GH levels. Optimal thresholds obtained from the ROC analysis suggested that lower POD1 and POD7 GH values provided good sensitivity and specificity for cure, despite modest predictive values. The model with the best ability to predict outcome included size, POD1 GH and POD7 GH levels, with a score of ≥95 demonstrating high specificity for prediction of remission.

Conclusion

Early postoperative GH assays are highly sensitivity and specific. The scoring system that we propose provided excellent predictive value and requires further validation in larger cohorts and in different populations. The model may help guide the intensity of follow-up and enable early identification of residual disease.     

Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of growth hormone-producing pituitary tumors

Stereotactic radiosurgery on the pituitary given with the cobalt-60 gamma unit was used in the treatment of 21 patients with growth hormone (GH)-producing pituitary adenomas and acromegaly. All but one patient had locally invasive macroadenomas, and in the majority of cases, there was parasellar growth. Radiosurgery was the initial treatment for seven patients. Fourteen patients were previously treated by pituitary surgery, eight of whom had undergone conventional external pituitary irradiation as well. All patients had clinical signs of active acromegaly before radiosurgery. The radiation doses given to the previously untreated patients or those who only underwent surgery were 40 to 70 Gy in each of one to three irradiations. The patients with previous external irradiation received a lower dose of 30 to 50 Gy in each of one or two irradiations. The patients were observed during a period of 1 to 21 years from the first radiosurgical session. Two young patients had a clinical remission with a substantial decline of GH levels to near normal serum profiles. Another eight patients obtained reduction of GH levels and clinical activity. More than half of the patients (11 of 21) had minor or no effects from the treatment. There were no complications from the radiosurgery except the development of pituitary insufficiency in 2 of 13 patients who did not undergo previous conventional external irradiation. The remission rates were lower than the results previously reported by us for radiosurgery for Cushing's disease. This may be a result of the predominance in the present study of invasive macroadenomas and single treatments and to the lower radiation doses used in the patients who underwent conventional irradiation previously.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathology of invasive pituitary tumors with special reference to functional classification

Pituitary adenomas may remain intrasellar or infiltrate dura and bone. Invasive adenomas are not considered to be malignant; in biological behavior they are between non-infiltrative adenomas and pituitary carcinomas. The latter are defined as tumors with subarachnoid, brain, or systemic metastasis. Invasion may be defined radiologically, operatively, or histologically. On the basis of operatively assessed tumor size and gross invasion of dura and bone as well as immunocytochemical and ultrastructural analysis of 365 pituitary adenomas, the following data were obtained. There were 23 growth hormone (GH)-cell adenomas: 14% microadenomas and 86% macroadenomas; their overall frequency of invasion was 50%. There were 24 prolactin (PRL)-cell adenomas: 33% microadenomas and 67% macroadenomas, with an overall frequency of invasion of 52%. Mixed GH-cell and PRL-cell adenomas were found in 35 cases; 26% were microadenomas and 74% were macroadenomas, and the overall frequency of invasion was 31%. Sixty patients had adrenocorticotropic hormone (ACTH)-cell adenomas (Cushing's disease): 87% microadenomas and 13% macroadenomas; the overall frequency of invasion was 25% (in 8% of microadenomas and 62% of macroadenomas). Twenty patients had ACTH-cell adenomas (Nelson's syndrome): 30% microadenomas and 70% macroadenomas; the overall frequency of invasion in these cases was 50% (in 17% of microadenomas and 64% of macroadenomas). Silent ACTH-cell adenomas, 100% macroadenomas, were found in 11 patients, with an 82% frequency of invasion. There were 32 follicle-stimulating and luteinizing hormone adenomas, all macroadenomas, with a frequency of invasion of 21%. Four patients had thyroid-stimulating hormone adenomas, all macroadenomas, with a 75% frequency of invasion. Null-cell adenomas were found in 93 cases: 2% microadenomas and 98% macroadenomas, with a frequency of invasion of 42%. There were 63 plurihormonal adenomas (GH, PRL, glycoprotein): 25% microadenomas and 75% macroadenomas, with a 50% overall frequency of invasion. Based on this study, and on their usual frequency of occurrence, the estimated rate of gross invasion by pituitary adenomas of all types is approximately 35%. It is concluded that immunocytochemical and ultrastructural characteristics of pituitary adenomas reflect the tendency of these tumors to infiltrate and hence may be of prognostic significance.     

Endonasal transsphenoidal approach for pituitary adenomas and other sellar lesions: an assessment of efficacy,safety, and patient impressions

OBJECT: The direct endonasal approach performed with the aid of an operating microscope for removal of pituitary tumors has the potential advantage over the traditional sublabial route of minimizing postoperative rhinological complications, yet maintaining a high degree of efficacy and safety. To assess the effectiveness of this procedure, tumor remission rates and surgical complications were documented, and patients' postoperative complaints were recorded using a questionnaire. METHODS: One hundred consecutive patients underwent 109 endonasal operations for tumor removal. At a median follow-up period of 16 months (range 3-45 months), surgical remission rates were as follows: in 40 patients with endocrine-inactive macroadenomas, 95% for noninvasive and 40% for invasive tumors; in the 20 patients with prolactinomas, 75% for prolactinomas with an initial prolactin (PRL) level lower than 200 ng/ml, 33% for those with a PRL level between 200 and 600 ng/ml, and 0% for those with a PRL level higher than 1400 ng/ml; in the 15 patients with Cushing disease, 73% for microadenomas and 25% for macroadenomas; in the 10 patients with acromegaly, 75% for microadenomas and 50% for macroadenomas; in the five patients with Rathke cleft cysts, 80%; and in the five patients with craniopharyngiomas, 40%. There were seven major surgical complications and no operative deaths. Among the 78 patients who completed questionnaires (response rate 89%), the most common complaints concerned nasal packing (39%), removal of packing (36%), and mouth breathing (35%). At 3 months or longer after surgery, patients quantified sinonasal problems as follows: for facial pain, no problem in 83% and severe difficulty in 4%; for nasal congestion, no problem in 74%, and severe difficulty in 3%; for decreased nasal airflow, no problem in 77% and severe difficulty in 4%; for decreased sense of smell, no problem in 73% and severe difficulty in 4%; and for upper-lip numbness, no problem in 87% and severe difficulty in 1%. Twelve (86%) of 14 patients who had undergone sublabial surgery previously preferred the endonasal approach in terms of pain and ease of recovery. CONCLUSIONS: The direct endonasal route for pituitary tumor removal has efficacy and complication rates comparable to those of the sublabial route. Patients generally recover rapidly from this minimally invasive procedure and have no or minimal sinonasal complaints. For patients requiring a repeated operation, the endonasal route appears to be less painful and easier to recover from than the sublabial route. Given the minimal nasal mucosal dissection required and the frequent patient complaints related to nasal packing, use of packing is no longer used for this procedure.     

Preoperative short-term administration of octreotide for facilitating transsphenoidal removal of invasive growth hormone-secreting macroadenomas

The somatostatin analog octreotide was administered prior to transsphenoidal surgery in three patients with tumors that extended to the suprasellar space and one side of the cavernous sinus. Octreotide, 100 micrograms twice a day, was subcutaneously injected for 2 weeks. Octreotide administration reduced the serum growth hormone (GH) levels in these patients from 82 to 22 ng/ml, from 148 to 12 ng/ml, and from 129 to 9 ng/ml. The tumor size shrank by about 50%, and the suprasellar extension disappeared in two patients. The main tumor was sharply dissected from the normal pituitary gland at surgery. Intracavernous portions were removed using a curette. Postoperatively, GH levels were less than 5 ng/ml in two patients, and 8.5 ng/ml in one patient. Follow-up magnetic resonance imaging revealed a small residual tumor in one side of the cavernous sinus in all patients. Follow-up GH levels were less than 5 ng/ml in one patient, and less than 2 ng/ml in two patients treated with bromocriptine. Preoperative administration of octreotide for 2 weeks reduced tumor volume and allowed near-total surgical resection of invasive macroadenomas without compromising the treatment course. Residual tumor due to intracavernous extension can be managed with bromocriptine or gamma knife radiosurgery.     

Clinical use of pre- and postsurgical evaluation of abnormal GH responses in acromegaly

The criteria by which acromegalic patients are considered "cured" after surgical therapy are still controversial. Since the abnormal growth hormone (GH) increase after the administration of some agents has been demonstrated to be characteristic of the tumoral somatotrophs, its disappearance after surgery may be taken as an index of the complete removal of the tumor. Serum GH increases after thyrotropin-releasing hormone (TRH, 200 micrograms intravenously), gonadotropin-releasing hormone (Gn-RH, 100 micrograms intravenously), and sulpiride (100 mg intramuscularly) injected during dopamine infusion (DA-Slp test), were evaluated in 68 acromegalic patients before and after transnasosphenoidal adenomectomy, and every 12 to 18 months during a follow-up period of 6 months to 11 years (average 42 months). Forty-two patients had abnormal responses to at least one test before surgery: 32 out of 68 (47%) to TRH, six out of 40 (15%) to Gn-RH, and 20 out of 28 (71%) to the DA-Slp test. Of 18 patients who underwent all three tests, 78% had abnormal responses to at least one of them. Twenty-three patients became unresponsive after surgery, and none of them had a recurrence or became abnormally responsive again during the follow-up period. Three out of six patients with postoperative serum GH levels between 5.1 and 10 ng/ml and three out of six patients with postoperative serum GH levels between 2.1 and 5 ng/ml remained abnormally responsive: one of them relapsed 1 year after the operation. The abnormal responses were lost in all 11 patients whose postoperative serum GH levels were below 2 ng/ml, and abnormal responses were maintained in all the patients in whom surgery was considered unsuccessful because postoperative serum GH levels were higher than 10 ng/ml. The TRH, Gn-RH, and DA-Slp tests should thus be considered useful tools in verifying the total removal of an adenoma. The reappearance of active acromegaly in the patient with low postoperative GH levels, who was still responsive to TRH, should be regarded as a reactivation and not a true recurrence of the disease.     

Differential effects of octreotide treatment and transsphenoidal surgery on growth hormone-binding protein levels in patients with acromegaly

OBJECT: The high-affinity growth hormone-binding protein (GHBP) represents the extracellular portion of the growth hormone (GH) receptor, and its serum levels are a reflection of the tissue receptor status. Levels of GHBP are decreased in patients with active acromegaly, probably because of downregulation of GH receptors. However, there are no studies of patients with acromegaly in which the effects of medical (that is, administration of somatostatin analogs) and surgical therapy on GHBP levels have been compared. That is the task the authors set out to accomplish in this study. METHODS: The authors studied seven patients in whom acromegaly had been recently diagnosed. They examined these patients at baseline, 2 months after octreotide treatment (subcutaneous administration of 100 microg octreotide three times per day), and 1 month after transsphenoidal surgery. Growth hormone-binding activity was measured, as well as the following biochemical markers of the somatotropic axis: GH suppression induced by oral administration of glucose, insulin-like growth factor-I (IGF-I), and insulin-like growth factor-binding protein-3 (IGFBP3). Although octreotide treatment induced a decrease in the levels of GH, IGF-I, and IGFBP3, as well as an increase in the level of GHBP, these biochemical markers did not reach normal levels. On the other hand, after transsphenoidal surgery, GHBP levels became normal, particularly in those patients in whom serum GH could be suppressed to an undetectable level after glucose loading. CONCLUSIONS: The authors conclude that persistently low GHBP levels in patients with acromegaly are normalized by successful pituitary surgery and correlate well with disease activity.     

Criteria for cure in acromegaly: report of a case apparently cured in which persisting tumor was found at autopsy

A 49-year-old man with acromegaly underwent the apparently complete removal of a pituitary microadenoma by the transsphenoidal route. There was complete remission of the biochemical abnormalities for 2 1/2 years, with basal plasma growth hormone (GH) levels of less than 1 ng/ml and normal somatomedin levels. The patient then died after the rupture of a cerebral aneurysm. Serial sections of the pituitary fossa showed persistent tumor with a volume of about 6% of the remaining normal gland. It is concluded that current endocrine tests are limited in their ability to detect residual GH-secreting tumor. Their sensitivity is likely to depend on the mass of tumor and on the GH secretion rate. Predictions of long term cure based on these tests are only tentative.     

Fully endoscopic transsphenoidal surgery for functioning pituitary adenomas: A retrospective comparison with traditional transsphenoidal microsurgery in the same institution

BackgroundThe efficacy and the minimally invasive nature of the fully transnasal endoscopic procedure in the treatment of pituitary adenomas and other lesions of the sellar area have been widely reported in the literature. Many authors observed similar results in terms of the correction of hormonal hypersecretion in functioning pituitary adenomas using endoscopic endonasal surgery or the traditional microscopic technique. We report the endocrinologic outcome in 2 series of patients operated on at the same institution for functioning pituitary adenomas using these 2 different techniques.MethodsThis study includes 2 successive series of 60 consecutive patients presenting with a hormonally active pituitary adenoma operated on by the same surgeon. The surgical results obtained in the most recently operated group using a fully endoscopic endonasal technique were compared with those obtained previously using the traditional microsurgical transsphenoidal procedure. The classification of tumors into 4 grades according to Hardy was based on modern MRI and intraoperative findings.ResultsThe overall remission rate of hypersecretion was 63% in the endoscopic group compared with 50% in the microsurgical group. The most obvious difference between the 2 groups was observed in noninvasive macroadenomas. In this specific grade of tumors, the remission rate of hypersecretion obtained using endoscopy was 78% compared with 43% using microsurgery. The endocrinologic results achieved for microadenomas were similar in the 2 groups. Postoperative CSF leaks occurred more frequently (6 cases) in the endoscopic group.ConclusionsIn our experience, fully endoscopic transsphenoidal surgery for functioning pituitary adenomas leads to a better endocrinologic outcome for noninvasive macroadenomas compared to the traditional microsurgical technique. However, morbidity with the endoscopic technique was higher in terms of the rate of postoperative CSF leaks.