Transsphenoidal Adenomectomy Research Articles

Transsphenoidal surgery for Cushing's disease: Results in 120 cases over a 23-year period

Transsphenoidal adenomectomy is the preferred treatment for Cushing's disease. We analyzed a group of 124 patients with presumed Cushing's disease who were treated by transsphenoidal microsurgical adenomectomy between 1972 and 1995. Of these, 24 patients had macroadenomas, 92 had microadenomas, 4 had corticotroph hyperplasia, 2 had Nelson's syndrome, and 2 had bronchial carcinoid tumors. Mean follow-up was 60 months (range 3-164 months). Chart review and current clinical and biochemical data were analyzed to determine remission and recurrence rates and predictors of outcome. Remission was achieved in 15 of 22 (68%) patients with macroadenomas and in 72 of 79 (91%) patients with microadenomas. Recurrent disease occurred in 5 of 15 (33%) patients with macroadenomas, with a mean time to recurrence of 16.2 months. Conversely, 7 of 72 (9.7%) patients with microadenomas experienced a recurrence, albeit with a longer mean time to recurrence of 54 months. This difference in disease-free survival between...

How (not) to diagnose growth hormone deficiency in adults: Stimulated serum concentrations of growth hormone in healthy subjects and in patients with pituitary macroadenomas

The secretion of growth hormone (GH) stimulated by GH-releasing hormone ([GHRH] 100 μg intravenously [IV]) was determined in 33 patients with nonfunctioning pituitary macroadenomas before and after transsphenoidal adenomectomy and in 28 controls. Patients who needed substitution therapy for at least one additional pituitary hormone presented with lower GH secretion than the remaining patients with pituitary tumors. However, there was a marked overlap of stimulated GH secretion between these two groups (3.2 ± 4.3 ng/mL and 7.2 ± 6.6 ng/mL, respectively) and between either group with the control group (7.1 ± 5.5 ng/mL). In an independent investigation, the effect of IV GHRH (100 μg) on the secretion of GH in seven healthy volunteers was shown to be comparable to that seen during an insulin tolerance test ([ITT] 0.1 U/kg IV). Thus, the GHRH stimulation test, a simple and comparatively unharmful procedure, is a useful alternative to the ITT in patients with potential pituitary defects. However, the pronounced overlap of stimulated serum GH concentrations in patients with pituitary macroadenomas and those estimated in healthy subjects and in patients with nonpituitary diseases underlines the difficulty in biochemically defining acquired GH deficiency in adults. We suggest that GH therapy in adults should primarily be instituted in patients with additional defects in anterior pituitary function.

Changes in serum cytokine concentrations after neurosurgical procedures.

Cytokine responses to surgical trauma have been studied in 70 patients undergoing various neurosurgical procedures. Serum concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8, (IL-8), tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured before and after surgery using enzyme-linked immunosorbent assays. The serum concentrations of IL-1 beta, IL-8, TNF-alpha, and IFN-gamma did not change significantly following neurosurgical operations. In contrast, serum IL-6 levels were significantly elevated following surgery, peaking at postoperative day 1 and then gradually decreasing. Maximum IL-6 concentrations were considerably higher in patients who underwent surgery for brain tumours or aneurysms as compared with patients who had a ventriculoperitoneal shunt, neurovascular decompression or transsphenoidal adenomectomy. Intra-operative use of methylprednisolone, which is known to block the production and action of cytokines, suppressed the increase in IL-6 levels after surgery. There was a statistically significant correlation between the IL-6 peak concentration and the length of surgery in patients not treated with steroids, but not in patients treated with steroids. Additionally patients who underwent supratentorial surgery had higher peak concentrations of IL-6 than those who underwent infratentorial surgery. These results suggest that IL-6 is an early marker of tissue damage and may be useful in assessing the extent of postoperative stress.

Transsphenoidal adenomectomy for microprolactinomas: 10 to 20 years of follow-up

Transsphenoidal adenomectomy is an effective treatment fo r microprolactinomas. However, postoperative recurrence of hyperprolactinemia is not rare. This study was designed to evaluate the long-term outcome of women with microprolactinomas operated on by transsphenoidal approach. We retrospectively studied 64 women with microprolactinomas who underwent transsphenoidal adenomectomy and were followed for 10 to 20 years. Postoperatively, 58 women (90%) had normal plasma prolactin concentrations (<20 microg/L). After a mean of 3.3 years, during which the women were asymptomatic with normoprolactinemia, 25 (43%) had a relapse of hyperprolactinemia (> or = 20 microg/L). However, their evolution varied. Fifteen women had symptomatic hyperprolactinemia. Computed tomography (CT) scans showed recurrent microadenomas in 2 women. The other 10 women had only hyperprolactinemia. Of these women, 5 had transient hyperprolactinemia (29 +/- 4 microg/L) for 5 years, after which prolactin declined to normal 13 +/- 3 microg/L). The remaining five patients had elevated prolactin (31 +/- 3 microg/L) throughout the follow-up period (10 to 20 years). CT scan did not show recurrent adenomas in these women. Thirty-three women remained normoprolactinemic and asymptomatic for a mean period of 12 years (range, 10 to 20 years). In conclusion, most of the patients with late relapse of hyperprolactinemia have slight functional hyperprolactinemia and remain asymptomatic with no evidence of tumor recurrence.

Transsphenoidal selective adenomectomy is the treatment of choice in patients with Cushing's disease. Considerations concerning preoperative medical treatment and the long-term follow-up.

Cushing’s observation, that most patients with the disease named after him harbor small basophilic pituitary adenomas, has been confirmed by the success of transsphenoidal surgery in the majority of patients. Monoclonality of such tumors supports the concept of a primary pituitary origin of the disease, which indeed then should be cured after their selective removal. It has become evident that ACTH secretion by the normal corticotrophs surrounding these microadenomas is suppressed in most cases and that this suppression persists for many months after the selective removal of ACTH-secreting microadenomas before a gradual normalization occurs. This initial period after surgery is accompanied by clinically evident hypocortisolism to a degree that is seldom achieved more thoroughly after surgery on other types of pituitary tumors. A gradual return to normal of the diurnal rhythm of ACTH and cortisol, of the response to an insulin-induced hypoglycemia, of daily adrenal cortisol production, as well as a return to normal sensitivity of the restored hypothalamopituitary adrenal axis to low dose dexamethasone supports the concept of a real cure in these patients. Most series describing the results of selective removal of ACTH-secreting tumors by transsphenoidal surgery report an overall percentage of immediate remission of about 75%. Amongst the therapeutic failures a small group of patients can be identified in whom the diagnosis of pituitary-dependent Cushing’s disease was wrong after all. This group includes individuals with occult tumors secreting ACTH and/or CRH ectopically, patients with primary glucocorticoid receptor resistance, and patients with secondary autonomous adrenocortical lesions. The majority of therapeutic failures, however, are neurosurgical. Several categories can be recognized: patients in whom extensive pituitary exploration did not reveal an adenoma, patients in whom the tumor could not be completely removed (in many of these cases invasive tumor penetration of bone or surrounding tissue made selective removal technically impossible), and finally an undetermined number of patients with a seemingly discrete lesion that was, in retrospect at microscopical examination, surrounded by hyperplastic corticotrophs. There is no ideal therapy for patients with Cushing’s dis

Expression of thyroid hormone receptors in human pituitary tumor cells.

To understand the expression of thyroid hormone receptors (TRs) in various types of pituitary tumor cells, we performed the reverse transcription coupled to polymerase chain reaction (RT-PCR). Specimens of pituitary adenomas were obtained by transsphenoidal adenomectomies from 2 patients with acromegaly, 6 patients with prolactinoma, 3 patients with Cushing's disease, 2 patients with gonadotropin-secreting tumors, one patient with a TSH-secreting tumor, and 3 patients with non-functioning adenoma with no clinical evidence of pituitary hormone overproduction. Human thyroid hormone receptors beta 1 and alpha 1, alpha 2 (h-TR beta 1, alpha 1, alpha 2) are expressed in nonfunctioning adenomas; h-TR alpha 1 and beta 1 are specific for prolactinomas; h-TR beta 1 is involved in acromegalies and FSH-secreting tumors, while h-TR alpha 1, alpha 2, and beta 1 are not expressed in TSH-secreting and ACTH-secreting tumors. The results suggest that human thyroid hormone receptors are differentially expressed in human pituitary tumor cells, and our studies have shed new light on the understanding of the role of TRs in pituitary tumors.

Characteristics of acromegalic patients with a good response to octreotide, a somatostatin analogue

In GH-secreting pituitary tumours somatostatin receptor density has been correlated with octreotide responsiveness. Little is known about the other endocrine characteristics of patients with good responses to octreotide. The purpose of this study was to determine the characteristics of these patients. We studied 30 patients with active acromegaly. Five had been treated with either transsphenoidal adenomectomy or conventional radiotherapy without cure of GH excess. Patients were divided into good or poor octreotide responders. Patients whose GH level decreased to less than 20% of basal and below 20 mU/I after a subcutaneous injection of 100 micrograms of octreotide were defined as good octreotide responders. We compared tumour size, basal GH secretory pattern, responses to TRH, GnRH and bromocriptine, and mutation of the alpha-subunit of stimulatory GTP-binding protein (G alpha s) between the two groups. Tumour size was determined by CT or MRI. Basal GH level was measured hourly between 0800 and 1600 h. GH responses to TRH and GnRH were measured every 30 minutes for 2 hours, and the GH response to oral bromocriptine was measured hourly for 6 hours. The mutation of G alpha s gene between codons 184 and 251 was examined by direct sequencing using PCR in 5 patients of each group whose tumour tissues were available for the genomic DNA extraction. Seventeen patients (57%) were good octreotide responders (group I) and 13 (43%) were poor responders (group II). The mean age, sex, tumour size, tumour grade and the basal GH secretory pattern were not significant different between the two groups. Group I responded more frequently than group II to TRH (65 vs 25%). Fifty-three per cent of group I patients and none of group II were good bromocriptine responders. Forty-one per cent of group I patients responded to both TRH and bromocriptine. Three of 5 group I tumours had point mutations at codon 201 of the G alpha s gene, none of 5 group II tumours had mutations. CGT(Arg) was replaced with TGT(Cys) in two tumours and with AGT(Ser) in one. No mutations were found at codon 227. All three tumours with mutations were from patients responsive to TRH. Two of the three were also good bromocriptine responders. These data suggest that good octreotide responders are more likely to respond to TRH or bromocriptine. Good octreotide responders may include subgroups with different levels of TRH and dopamine receptor expression. A possible relation between octreotide response and the mutation of G alpha s gene should be investigated.

Pituitary function after selective adenomectomy for Cushing's disease.

This retrospective analysis was undertaken to determine whether selective adenomectomy for Cushing's disease can achieve acceptable cure rates while causing minimal pituitary dysfunction. Tumour size, histology and pituitary function were evaluated in 34 consecutive patients (26 F:8 M, mean age 33.6 years) undergoing transsphenoidal adenomectomy for Cushing's disease from 1975 to 1992. Follow-up averaged 5.8 years. Cure was defined as resolution of symptoms and signs and normalization of urinary cortisol excretion. Sixty-three per cent of patients achieved cure after selective adenomectomy; repeat adenomectomy cured an additional four patients. Twenty-eight per cent required bilateral adrenalectomy and/or pituitary irradiation. Postoperative pituitary function remained completely intact in 81%. Secondary hypogonadism occurred in 8%, hypothyroidism in 15% and permanent diabetes insipidus in 4%. There was recurrence in 26% after a mean of 4.6 years (range 1-7). It is concluded that selective adenomectomy can achieve acceptable cure rates with a low prevalence of postoperative hypopituitarism, although an increase of recurrence may be the result of conservative surgery.

Serum lipoproteins in acromegaly before and 6-15 months after transsphenoidal adenomectomy.

Acromegaly is a rare disorder characterized by over-secretion of GH, most often because of a pituitary adenoma. The disease is associated with disturbances in lipoprotein metabolism and an increased cardiovascular mortality. The aim of the present study was to investigate whether treatment of acromegaly results in changes in serum concentrations of lipids and apolipoproteins, including lipoprotein(a) (Lp(a)). Fourteen patients with clinical features of acromegaly and increased GH secretion were studied 1-10 months before and 6-15 months after transsphenoidal adenomectomy in an open study. Three patients had diabetes mellitus before surgery and two of these patients had normalized serum glucose levels post-operatively. Mean and baseline plasma GH levels were determined from 24-hour GH profiles. Serum samples were taken in the morning after an overnight fast. All patients were normocholesterolaemic, and four patients were hypertriglyceridaemic before treatment. Mean plasma GH levels decreased from 34.5 +/- 7.4 to 2.1 +/- 0.4 mU/l (mean +/- SEM). Serum IGF-I, insulin and free T3 levels decreased and serum SHBG concentrations increased post-operatively. There was no effect of treatment on serum cholesterol concentrations, but serum triglyceride concentrations decreased. Serum apolipoprotein (apo) B and apoE levels were unaffected by treatment. Serum apoA-I levels increased and Lp(a) levels decreased post-operatively. Successful treatment of acromegaly, resulting in normal mean GH values (< 5 mU/l) and/or normal responsiveness to TRH, have beneficial effects on serum lipoproteins with increased serum apoA-I levels and decreased serum levels of triglycerides and Lp(a). These effects seem to be independent of improvement in glucose tolerance, since patients with diabetes mellitus before surgery and normal fasting blood glucose levels post-operatively had similar lipoprotein responses to treatment as those with normal fasting blood glucose levels before surgery.

Factors determining the long-term outcome of surgery for acromegaly

Seventy-nine patients with acromegaly were investigated before and after transsphenoidal adenomectomy, to determine the immediate and late outcome, the pre-operative features associated with a good result, and the accuracy of post-operative testing in predicting outcome. Pre-operative evaluation included basal growth hormone (GH), GH response to oral glucose tolerance test (OGTT), GH response to thyrotrophin-releasing hormone (TRH), tests of pituitary reserve, and pituitary scanning to assess tumour size. A few weeks after surgery, these tests were repeated. The patients were recalled for late assessment 1-13 years (median 86 months) after the operation. At the immediate postoperative testing, minimum GH after oral glucose was < or = 2 mU/l in 48.7%, < 5 mU/l in 76.3% and < 10 mU/l in 84.2%. Only 12 patients had GH > 10 mU/l. Basal GH was < or = 2 mU/l in 21%, < 5 in 59.2%, < 10 in 73.6% and < 20 in 90.8%. A minimum GH of < or = 2 mU/l during an OGTT was achieved in 67.4% of patients with intrasellar tumours, compared with 27.3% with extrasellar tumours. Basal GH and post-glucose GH correlated with the late outcome. GH response to TRH showed no correlation with outcome. IGF-1, which could not be assessed in detail, correlated with GH but was not a reliable indicator of outcome. Transsphenoidal adenomectomy is thus a very satisfactory treatment for acromegaly. Postoperative levels of basal growth hormone < 5 mU/l and post-glucose GH < or = 2 mU/l can be regarded as a biochemical cure. Postoperative radiotherapy is not required in patients who achieve a good result. The preoperative factors which significantly influenced the final outcome were basal GH, post-glucose minimum GH, tumour size and impaired pituitary reserve.

Immediate recovery of pituitary function after transsphenoidal resection of pituitary macroadenomas.

Mild hyperprolactinemia frequently accompanies the hypopituitarism associated with pituitary macroadenomas not secreting PRL. Because of this association, hypopituitarism was postulated to be due to compression of portal vessels. We postulate that resumption of hypothalamic control over pituitary function occurs immediately after adenomectomy. To test this hypothesis, we examined pituitary function before and after transsphenoidal adenomectomy in 26 ACTH-deficient patients and 23 subjects with normal adrenal and thyroidal functions (control group). Glucocorticoids, given only to ACTH-deficient subjects, were withdrawn 36 h after surgery. ACTH, cortisol, and PRL levels were measured twice daily in all patients. Both ACTH and PRL levels increased hours after surgery in controls and returned to baseline over 4 days. In all hypopituitary subjects, PRL levels decreased by 50% within hours of adenomectomy and remained so until discharge. ACTH levels, measured simultaneously, increased within hours in 17 of 26 hypopituitary patients, all of whom recovered normal adrenal function before discharge. Nine additional patients had low ACTH levels and required cortisol replacement. The reciprocal changes in PRL and ACTH levels measured simultaneously, hours after surgery, support the hypothesis that hypopituitarism is reversible and largely caused by compression of the protal vessels and the resulting interruption of delivery of hypothalamic hormones. The persistence of hypopituitarism in some patients suggests that ischemic necrosis of the anterior pituitary could limit recovery.

Effect of corticotrophin-releasing hormone administration on growth hormone levels in acromegaly: in vivo and in vitro studies.

The ability of CRH to cause a paradoxical response of GH in acromegaly is still under debate. In this study, the effect of CRH administration on GH release was evaluated in a large series of patients with active acromegaly, both in vivo, compared to that of TRH and GnRH, and in vitro. The study was organized as follows. In vivo study: 30 acromegalic patients were submitted to TRH, GnRH, and CRH tests on non-consecutive days: blood samples were collected before and 10, 20, 30, 45, 60, 90, and 120 min after bolus. In nine patients the CRH test was repeated after a 3-month therapy with octreotide and at the dose of 300-600 micrograms sc thrice daily. In vitro study: CRH (10 nmol/l, 100 nmol/l, and 1 mumol/l) was tested on pituitary tumor tissue obtained in eight patients during transsphenoidal adenomectomy and immediately placed in sterile Ca2+ and Mg2+ free buffer phosphate. A paradoxical GH response to TRH (evaluated as a GH increase over 50% of basal values) was recorded in 19 patients (63.3%), whereas 7 patients (23.3%) responded to GnRH and 4 others to CRH (13.3%). TRH administration induced a maximal percent GH increase significantly greater than that induced by GnRH and CRH (p < 0.05). Octreotide caused the normalization of GH and insulin-like growth factor-I levels in all the patients, as well as the disappearance of the GH paradoxical response to CRH in 3/4 patients. All four CRH responders and four CRH non-responders, used as controls, were surgically treated and adenomatous tissue was used for the in vitro study.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile gonadotrophin-releasing hormone therapy in patients with pituitary tumours treated by surgery and irradiation.

Pulsatile administration of GnRH for induction of ovulation is effective for women with idiopathic hypogonadotrophic hypogonadism. We were interested to assess the pituitary-ovarian response to pulsatile GnRH infusion and the therapeutic effectiveness of restoring ovulation in a group of hypogonadotrophic women previously treated with surgery and irradiation to pituitary tumours. The group of patients comprised 15 hypogonadotrophic women, aged 29-40 years (mean 32.4 years), who had undergone transsphenoidal adenomectomy or craniotomy and irradiation with a total of 4500-5400 cGy in 25 fractional doses divided over 5-6 weeks. The time interval from irradiation to study was 6.3 +/- 2.0 years (mean +/- SD). A single bolus GnRH (100 micrograms) test and pulsatile infusion of GnRH were performed to assess the pituitary gonadotrophin reserve and induce ovulation. We tried to correlate the pituitary response with characteristics of intracranial lesions on computerized tomography findings. We undertook ovarian biopsy in one patient who failed to respond to gonadotrophin therapy and pulsatile infusion of GnRH. Twelve women (80%) showed evidence of ovulation in response to pulsatile GnRH treatment and five subsequently became pregnant. Four of 12 ovulators were previous non-ovulators to exogenous gonadotrophin therapy. There was no correlation between pituitary response and character of lesions based on computerized tomography findings. A patient who failed to respond to either gonadotrophin or pulsatile infusion of GnRH had premature ovarian failure on ovarian histology. The functional reserve capacity of pituitary gonadotrophs may remain less impaired by tumour encroachment, pituitary surgery or irradiation than had previously been thought. This holds promise for ovulation induction in hypogonadotrophic patients who had been treated with surgery and irradiation for pituitary tumours.

THE SECRETORY DYNAMICS OF GROWTH HORMONE IN PATIENTS WITH CUSHING DISEASE

Growth retardation to complete growth arrest is the hallmark of Cushing syndrome in children. The major mechanism for this has been considered the glucocorticoid-induced resistance of target-tissues to insulin-like growth factor 1 (IGF-1) and other growth factors. The purpose of this study was to examine the growth hormone (GH) secretory dynamics of patients with Cushing disease before and up to 12 months after their cure by transsphenoidal adenomectomy. In fourteen patients, every 20 minutes blood sampling during 24h for determination of plasma GH was performed. These patients also underwent arginine infusion and L-Dopa stimulation tests. Fourteen sex-and pubertal stage- matched normal volunteers were used as controls. Prior to therapy, the patient group had an increased BMI (31.5 ± 5 kg/m2) and markedly decreased plasma 24h GH mean, peak amplitude and peak area values, with pulse frequency similar to that of the controls. GH values after arginine and L-Dopa stimulation were also subnormal in many of these patients with 2 out of 8, and 8 out of 10 failing to show GH responses greater than 7 ng/ml in the respective test. Surprisingly, the same pattern of GH suppression was observed in the patients who were studied 10-11 days, 3 months and 6 to 12 months after their cure, when their BMIs were respectively, relatively stable, 26.9 ± 3.8 kg/m2, and 24.8 ± 3.3 kg/m2. These findings suggest that patients with Cushing disease have marked GH suppression during their illness, which continues for at least a year during their convalescence. We conclude that frank GH deficiency may be another important mechanism for the growth retardation observed in children with Cushing syndrome. In view of the persistent GH suppression after curative removal of the pituitary adenomas, patients should be clinically evaluated for the potential need for GH replacement.

TRH/GnRH Test in Acromegaly

We investigated the rate of recurrence in acromegaly in 20 patients who were found to have a TRH and GnRH induced GH response postoperatively after primarily successful transsphenoidal selective adenomectomy in a retrospective study. All operations had been carried out by the same neurosurgeon (R.F.). Successful therapy was defined as basal GH-levels < or = 2 ng/ml and no evidence of residual tumour in the postoperative neuroradiological examination. The follow-up period ranged from 5 to 14 years (mean 7.7 years). At the last follow-up visit an OGTT was performed and SmC measured. In spite of the long-follow-up period we did not find patients with recurrent acromegaly in this investigation. We conclude that, in contrast to previous studies, a stimulation of GH in the TRH/GnRH test does not necessarily predict likely recurrence of acromegaly in patients with an adequate suppression of GH during an OGTT following operative microsurgical treatment.

Diagnosis and surgical treatment of microcorticotropinomas

Microsurgical selective removal of hypophyseal adenomas is more and more frequently used in the treatment of Itsenko-Cushing's disease of late. This permits complete cure of approximately 90% of the patients. Ten patients with this disease, induced by corticotropinoma, were observed. The hormonal methods, as well as computer-aided tomography and NMR tomography, were used to diagnose the condition. A high resolving power of these methods for the diagnosis of this disease is noteworthy. The authors describe the method for microadenoma detection during the operation and present the data of hormonal studies after selective adenomectomy. They emphasize that in cases when clinical data are supported by the hormonal and x-ray findings that confirm the presence of a microcorticotropinoma in Itsenko-Cushing's disease transsphenoidal adenomectomy must be the method of choice for the treatment of such patients.

Transsphenoidal adenomectomy for growth hormone-secreting pituitary adenomas in acromegaly: outcome analysis and determinants of failure.

The results of transsphenoidal adenomectomy for growth hormone (GH)-secreting pituitary adenomas in acromegaly performed over a 17-year period were analyzed retrospectively to determine which preoperative factors significantly influenced the long-term surgical outcome. These variables were then used to develop a logistic regression model to determine the probability of surgical failure. The series consisted of 103 patients. Long-term follow-up study (mean duration 102 +/- 64 months) was performed to derive outcome analysis and determinants of failure. Surgical control was defined as a long-term postoperative serum basal GH level of less than 5 micrograms/liter, a long-term postoperative serum somatomedin C (SM-C) level of less than 2.2 U/ml, and a favorable clinical response. Eighteen (17.5%) patients did not meet these criteria. The overall control rate by the GH criteria was 81.3% and by the SM-C criteria 76.2%. By multivariate logistic regression analysis, tumor stage was the strongest predictor of outcome (p < 0.05). The preoperative GH level, tumor grade, and preoperative SM-C level were significant univariate predictors (p < 0.05). There were statistically significant differences in mean preoperative GH and SM-C levels (p < 0.05, t-test) and tumor stage (p < 0.05, chi-squared test) between patients whose acromegaly was controlled by surgery and those whose acromegaly was not. Furthermore, estimates were derived of the probability of surgical failure based on preoperative GH level, preoperative SM-C level, and tumor grade and stage. The authors believe these findings will enhance clinical decision-making for neurosurgeons considering transsphenoidal microsurgery in patients with acromegaly.

Expression of Growth Hormone (GH)-Releasing Factor Gene in GH-Producing Pituitary Adenoma

Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.

Treatment of macroprolactinomas with the long-acting and repeatable form of bromocriptine: a report on 29 cases.

Twenty-nine patients with macroprolactinomas were treated by monthly intramuscular injections of the long-acting and repeatable form of bromocriptine (Parlodel-LAR) in doses ranging from 50-150 mg. They were divided into two groups: group I consisted of 22 patients who received Parlodel LAR before transsphenoidal adenomectomy; group II was composed of 7 patients with earlier neurosurgery and of 2 patients from group I not cured by transsphenoidal adenomectomy. Duration of therapy varied from 1-12 months, and a total of 104 injections was given. At nadir day, serum PRL levels were situated between less than 1% and 43% of pretreatment values. At day 28 after the first injection, serum PRL levels varied between less than 1% to 139% of initial values. No difference could be detected between the two groups regarding the percent of PRL inhibition. Long-term treatment with Parlodel-LAR resulted in a sustained inhibition of PRL secretion, except for 1 case. Resumption of menstrual cycles occurred in 4 out of 15 women and correction of hypogonadism in 4 out of 14 men. Amelioration of disturbed visual fields was recorded in 3 out of 8 patients. Diminution of the adenoma volume was radiologically documented in 14 out of 22 cases. Only few and mild side effects were recorded. One patient with partial adrenal deficiency suffered from a syncope, but this was prevented by hydrocortisone supplementation during the subsequent Parlodel-LAR administration. In conclusion, Parlodel-LAR proved effective in the treatment of macroprolactinomas, achieving rapid inhibition of PRL secretion, and in some patients amelioration of hypopituitarism, reduction in tumor size, and improvement in visual fields, and caused no serious side effects. It is a valuable preparation to surgery and can also be used in long-term medical therapy.

Expression of growth hormone (GH)-releasing factor gene in GH-producing pituitary adenoma.

Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.