This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferone, D. Articles by Lombardi, G. Search for Related Content PubMed PubMed Citation Articles by Ferone, D. Articles by Lombardi, G.

Correlation of Scintigraphic Results Using ¹²³I-Methoxybenzamide with Hormone Levels and Tumor Size Response to Quinagolide in Patients with Pituitary Adenomas

Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University (D.F., A.C., G.C., B.M., G.L.), Department of Nuclear Medicine, National Cancer Institute, "Fondazione G. Pascale" (S.L., P.V., W.A.), CNR (M.S.), 080131 Naples, Italy.

Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University, via S. Pansinis, 80131 Naples, Italy.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The efficacy of dopaminergic agents in the medical treatment of pituitary adenomas is well known. Quinagolide is a nonergot derivative dopamine agonist, which binds dopamine D₂ receptors with high affinity. The treatment with this drug is reported to suppress hormone levels and to cause tumor shrinkage in prolactinomas and in a few GH-secreting pituitary adenomas. In clinically nonfunctioning pituitary adenomas (NFPA), the efficacy of quinagolide treatment is controversial. The scintigraphy of the pituitary region using ¹²³I-methoxybenzamide (¹²³I-IBZM) allows us to visualize in vivo the expression of dopamine D₂ receptors on pituitary tumors.

In this study, the pituitary scintigraphy with ¹²³I-IBZM was performed in 14 patients with macroadenoma before starting a long-term treatment with quinagolide: 6 NFPA with high circulating -subunit levels, 4 PRL-secreting, and 4 GH-secreting adenomas. A 3-point score was used to grade the ligand accumulation within the pituitary adenomas: 0 = negative, 1 = moderate uptake (equal to that recorded in the cerebral cortex), and 2 = intense uptake (equal to that recorded in the basal nuclei). The treatment with quinagolide was carried out at the dose of 0.3–0.6 mg/day for 6–12 months. Clinical, biochemical and hormonal assessment was repeated monthly during the first 3 months, then quarterly. Sellar magnetic resonance imaging was performed before and after 6 and 12 months of quinagolide treatment, to evaluate tumor shrinkage (>25% of baseline size).

In all 14 patients, a significant positive correlation was found between the degree of ¹²³I-IBZM uptake and the clinical response to quinagolide treatment (r = 0.90; P < 0.001). In particular, the normalization of serum -subunit and PRL levels, respectively, was achieved in 3 patients with NFPA and in 2 patients with prolactinoma, who showed intense ¹²³I-IBZM uptake in the pituitary region. In 4 of these 5 patients with positive scan, a significant tumor shrinkage occurred between 6 and 12 months after the beginning of quinagolide treatment. In all patients with GH-secreting adenoma, no significant uptake of ¹²³I-IBZM was found and no significant decrease of circulating GH and/or insulin-like growth factor-I levels, and tumor shrinkage was obtained during long-term treatment with quinagolide.

In conclusion, the pituitary scintigraphy with ¹²³I-IBZM can be considered a useful tool to indicate adenomas with significant expression of functioning D₂ receptors. This innovative technique may predict the response to long-term treatment with quinagolide in patients with NFPA, where the lack of pituitary hormone hypersecretion makes difficult the monitoring of medical treatment efficacy.

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
DOPAMINE-AGONISTS represent the first choice for medical treatment of prolactinomas, causing the normalization of serum PRL levels approximately in 90% of patients and producing tumor shrinkage in 60–70% of them (1). Conversely, these agents normalize circulating GH and insulin-like growth factor-I (IGF-I) levels only in 20–40% of acromegalic patients (2, 3). Controversial data have been reported on the efficacy of long-term treatment with dopamine-agonists in patients with clinically nonfunctioning pituitary adenomas (NFPA) (1). These tumors include a heterogeneous class of different histotypes, namely glycoprotein-, - and ß-subunit-secreting tumors, oncocytomas, and null cell adenomas (4, 5). In recent years, quinagolide, a nonergot derivative dopamine agonist, which binds with high-affinity dopamine D₂ receptors (6), has been successfully employed in the treatment of hyperprolactinemic patients. Quinagolide was shown effective also in patients poorly responsive, and even resistant, to bromocriptine treatment (7, 8). In addition, the long-term treatment with quinagolide was reported effective in normalizing circulating GH and/or IGF-I levels in a few patients with acromegaly (3, 9, 10) and with NFPA (11). Because in patients with NFPA, the lack of hormone hypersecretion makes the treatment monitoring difficult, the possibility to select responsive patients before performing long-term trials could be helpful to avoid disappointing results.

In neurological diseases, the scintigraphy with ¹²³I-methoxybenzamide (¹²³I-IBZM), a specific ligand for dopamine D₂ receptors, was recently used to define the biochemical changes in receptor contents (12). In selected cases, ¹²³I-IBZM significantly accumulates in PRL-secreting adenomas, and the positive scintigraphic scan allows us to distinguish pituitary adenomas and other tumors located in the sellar region or in parasellar spaces (13). In a recent study, a significant correlation between the ¹¹¹In-diethylenetriamine pentaacetic acid (DTPA)-D-Phe¹-octreotide pituitary uptake and the response to long-term treatment with octreotide was found in patients with GH-secreting adenomas (14). Similarly, in two patients with prolactinoma, the response to long-term treatment with bromocriptine was significantly correlated with ¹²³I-IBZM pituitary uptake (15). By contrast, no correlation was found between the ¹¹¹In-DTPA-D-Phe¹-octreotide and ¹²³I-IBZM pituitary uptake and the response to treatment with octreotide and bromocriptine in a patient with mixed TSH/PRL-secreting pituitary adenoma (16). In this latter study, however, the dose of octreotide was probably inadequate and a nonselective D2-agonist was used.

The aim of the present study was to evaluate whether the in vivo D₂ receptor expression detected by ¹²³I-IBZM scintigraphy was useful to select patients with pituitary adenoma responsive to long-term treatment with quinagolide. For this purpose, the ¹²³I-IBZM pituitary scintigraphy was carried out before starting quinagolide treatment in six patients with NFPA and high-circulating -subunit levels, four patients with prolactinoma, and four with GH-secreting adenoma who served as control.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patients

Fourteen patients with pituitary macroadenoma gave their informed consent before being enrolled in this study. Six had diagnosis of NFPA and were selected from a large series of patients because of high circulating -subunit levels (from 2.6–5.1 IU/L). All these patients had been previously operated on, and the immunostaining was positive for FSH, LH, and TSH in 3, FSH and GH in 2, and negative in the remaining patient. After surgery, all the patients showed an evident residual tumor at sellar magnetic resonance imaging (MRI). Primary hypothyroidism and hypogonadism were excluded. In 4 patients with prolactinoma (serum PRL levels ranged from 190–396 µg/L), MRI documented an intrasellar macroadenoma in 3 and an intra- and suprasellar macroadenoma in the remaining patient. In 4 patients with GH-secreting adenoma (serum GH levels ranged from 20–56 µg/L, not suppressible below 2 µg/L after glucose load; and plasma IGF-I levels ranged from 330–600 µg/L), MRI documented an intrasellar macroadenoma in 2, an intra- and parasellar macroadenoma in 1, and a left parasellar residual tumor in 1. Bitemporal hemianopia was recorded by visual perimetry in 2 patients with prolactinoma. Clinical, hormonal, radiological, and scintigraphic results of the 14 patients are shown in Table 1.\.

All patients were treated with quinagolide for 6–12 months at a dose of 0.3–0.6 mg/day. The drug was given once daily at 1900 h, after dinner (0.3 mg, in patients with prolactinoma), or twice daily at 0100 h and 1900 h, after lunch and dinner (0.6 mg, in patients with NFPA and acromegaly), as previously described (3). Patients were considered responsive to the treatment when the normalization of elevated circulating hormones was achieved.\.

Protocol of the study

At study entry, all patients were submitted to clinical evaluation, standard laboratory evaluations (such as complete blood count, serum calcium, urea, uric acid, glucose, total protein, albumin, total and direct bilirubin, total cholesterol, alkaline phosphatase, serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sodium, potassium, creatinine, standard urine analysis and hormonal assessments, visual perimetry, sellar MRI, and ¹²³I-IBZM scintigraphy). The clinical, biochemical, and hormonal evaluation was repeated monthly during the first 3 months, then quarterly; visual perimetry was repeated quarterly during treatment in the 2 patients with visual field defects. Sellar MRI was repeated after 6 and 12 months, during treatment, to evaluate tumor size modifications. Tumor shrinkage greater than 25% of baseline size was considered significant.\.

¹²³I-IBZM study. Planar and single-photon emission computed tomography (SPECT) images of the head were obtained at 2–3 h after the injection of 185 Mbq 3-iodo-6-methoxybenzamide (specific activities ranged from 192–222 Mbq, Cygne BV, Eindhoven, The Netherlands). The labeling was performed according to the manufacturer’s recommendations. Quality controls were carried out on labeled compound before the injection, according to the manufacturer’s instructions (17). The studies were performed by a single (Orbiter II) or double-head camera (Solus, Adac Lab, Milpitas, Ca.) equipped with a high-resolution low-energy collimator [acquired 64 images, 50 sec each, matrix 64x64 without zoom factor, by a clockwise rotation of 360° with energetic window settled at 20% of ¹²³I photopeak (159 keV)]. The cameras were connected with a dedicated Sun Sparc-20 station. Reconstruction of the images was performed along the canto-mental line, by a Butterworth prefilter (0.5 cycles/cm cut-off and power factor 10) and a Ramp filter with attenuation correction. For visual analysis, transaxial images were obtained by adding three one-pixel slices, matrix 64x64. A 3-point score was used to grade the ligand accumulation within the pituitary adenomas. This was arbitrarily designed to qualitatively define the uptake: 0 = negative, 1 = moderate uptake (equal to that recorded in cerebral cortex), and 2 = intense uptake (equal to that recorded in the basal nuclei).

MRI study. MRI (1.0 Tesla, Magnetom, Siemens, Erlangen, Germany) was carried out by a superconductive magnetic resonance with T1-weighted SE sequences, 3-mm slides in coronal and sagittal sections, before and after contrast enhancement with Gadolinium-DTPA.

Visual perimetry study. The visual field examination was performed by the Goldmann and Friedman perimetry system. (Maag-Streit, Bern, Switzerland)

Assays

Serum GH and PRL levels were assayed by RIA using kits provided by Radim (Pomezia, Italy). The normal range of GH was below 5 µg/L, and the intra- and interassay coefficients of variation (CV) were 6.5 and 6.7%, respectively. Serum PRL levels were assayed by RIA using kits provided by Radim. The normal range of PRL was 5–20 µg/L, and the intra- and interassay CVs were 5 and 7%, respectively. Plasma IGF-I levels were assayed by immunoradiometric assay using kits provided by Eurogenetics (Turin, Italy). The normal range was 90–210 µg/L, and the intra- and interassay CVs were 7 and 16%, respectively. Serum -subunit levels were assayed by RIA using kits provided by Biomerica, IMC (Newport Beach, CA). The normal range was 0.1–1.5 IU/L for males and premenopausal females, and 0.7–4.4 IU/L for postmenopausal females, and the intra- and interassay CVs were 1.1 and 6.8%, respectively.

Statistical analysis

Data are reported as mean ± SEM. The statistical analysis was performed by the Student’s t test for paired data. The linear correlation analysis was carried out between percent hormone suppression and ¹²³I-IBZM score recorded within the pituitary adenomas. In the acromegalic group, only serum GH levels were taken into consideration for the correlation analysis. The significance was set at 5%.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Scintigraphic results

Brain SPECT images, 2 h after the iv injection of ¹²³I-IBZM, showed a very intense tumor uptake (score 2) in two of six patients with NFPA (nos. 1 and 4, Table 1) and in two of four with prolactinoma (nos. 8 and 10, Table 1). A moderate tumor uptake (score 1) was detected in one patient with NFPA (no. 3) and two patients with prolactinoma (nos. 7 and 9). The remaining seven patients showed a significant uptake of ¹²³I-IBZM only in the basal nuclei and were considered negative. In Fig. 1, two exemplary cases with negative and intense ¹²³I-IBZM uptake in the pituitary region, in comparison with MRI, results are shown.

View larger version (130K): [in this window] [in a new window]   Figure 1. MRI in coronal section (left) and SPECT with 123I-IBZM (right) in two exemplary patients with pituitary adenoma. Patient with acromegaly (no. 13, Table 1) with negative 123I-IBZM scan (top) and patient with prolactinoma (no. 8, Table 1) and positive 123I-IBZM scan (bottom). The arrows indicate the pituitary region.

During quinagolide treatment, circulating -subunit levels significantly decreased in all the patients with NFPA (P < 0.05, Table 1), being normalized in 3 patients (nos. 1, 3, and 4). Circulating -subunit levels decreased from 3.1 ± 0.3 to 0.2 ± 0.1 IU/L. Two of these three patients had score 2 at ¹²³I-IBZM scintigraphy and had a significant adenoma shrinkage after 6 and 12 months of quinagolide treatment, respectively (nos. 1 and 4, Table 1). In the third patient with score 1 (no. 3), a nonsignificant reduction in tumor size was measured at the end of treatment. Tumor size was unchanged in the remaining three patients. In all four patients with PRL-secreting adenomas, serum PRL levels were significantly reduced during quinagolide treatment. However, normoprolactinemia was achieved only in two patients who showed ¹²³I-IBZM uptake scored 2, after long-term treatment with quinagolide at a dose of 0.3 mg/day. In both patients, a significant shrinkage was documented by MRI after 6 months of quinagolide therapy. In the remaining two patients with ¹²³I-IBZM uptake scored 1, quinagolide caused a decrease of serum PRL levels without any significant tumor size modification after 12 months of therapy.

All four patients with GH-secreting adenomas had negative scintigraphic results. No significant decrease of circulating GH and IGF-I levels was obtained after 6–12 months of quinagolide treatment, and no change of tumor size was documented at MRI.

A significant positive correlation was found between scintigraphic results analyzed as uptake score and percent hormone suppression during quinagolide treatment (r = 0.90; P < 0.001).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Dopaminergic compounds are greatly effective in normalizing PRL levels and shrinking tumor mass in patients with prolactinoma but display only a minor effect in patients with GH-secreting adenomas and NFPA (1). Usually, NFPA are the tumors with the largest size, and often the residual anterior pituitary function is compromised either by direct compression or by interference with the mechanisms of the hypothalamic control (1). Therefore, tumor decompression is required, particularly if visual field defects occurred. The decompression is usually obtained via transsphenoidal route. However, this technique seldom cures large pituitary tumors when given alone, and radiotherapy is frequently applied, after surgery, to control tumor regrowth (18, 19). Moreover, the effect of radiotherapy develops slowly, hypopituitarism frequently occurs, and repeated endocrine evaluations are needed (20). For these reasons, the possibility to prevent or delay tumor regrowth, using medical treatment, is hopeful; but the results of pharmacotherapy in NFPA often have been disappointing. Long-term octreotide treatment was shown to be effective in a minority of patients with NFPA (21, 22, 23) and has high cost. Moreover, no correlation was reported between the results of ¹¹¹In-DTPA-D-Phe¹-octreotide scintigraphy and the tumor shrinking effect of long-term treatment with octreotide in NFPA-bearing patients (24). Among dopaminergic drugs, bromocriptine was used in NFPA with scant effects, despite the in vitro evidence of dopamine receptors on these tumors (1). However, dopamine D₂ receptors in NFPA were shown in a smaller amount and with a lower affinity than in prolactinomas (25, 26). Therefore, it is likely that patients with NFPA require long-term and high-dose bromocriptine treatment, which may cause severe side effects (1). In a series of NFPA-bearing patients, the treatment with quinagolide, at a dose of 0.3 mg/day for 1 year, was shown to be effective in reducing serum gonadotrophin and -subunit levels, improving visual fields defects, and producing significant tumor shrinkage (11).

Starting from the observation that the visualization of dopamine D₂ receptor expression can be obtained using ¹²³I-IBZM, a specific ligand for D₂ receptors (12), we investigated whether the degree of ¹²³I-IBZM uptake could predict the response to long-term treatment with quinagolide in patients with NFPA. For this purpose, we performed the scintigraphy with ¹²³I-IBZM before starting quinagolide treatment in a small group of patients with NFPA, characterized by having high -subunit levels, to biochemically monitor the effects of treatment. As control group, patients with GH- and PRL-secreting adenomas were used. The results of the present study showed a significant positive correlation between the scintigraphic results analyzed as uptake score and the hormone suppression after quinagolide treatment, evaluated as percent decrease of baseline secretion. Moreover, in all patients showing intense ¹²³I-IBZM uptake within pituitary adenoma, the normalization of hormone levels and the shrinkage of tumor mass were achieved after 6–12 months of treatment with quinagolide at a dose of 0.3–0.6 mg/day. These results are in agreement with those reported by Scillitani et al. (15) and de Herder et al. (13) in prolactinomas. Conversely, they are partially in contrast with those reported in a patient with mixed TSH/PRL-secreting adenoma, although it should be considered that this patient was treated with bromocriptine, which is a nonselective D₂ agonist (16). It also should be pointed out that in none of the previous studies on the use of ¹²³I-IBZM scintigraphy in pituitary adenomas, were patients with NFPA and high-circulating -subunit levels included.

In conclusion, the results of the present study suggest that intense ¹²³I-IBZM uptake in the pituitary adenoma may predict the successful response to long-term treatment with quinagolide in patients with NFPA and high-circulating -subunit levels and in those with PRL-secreting adenoma. The high cost of this radiotracer (approximately $1000 per dose) makes this approach unnecessary in patients with PRL- or GH-secreting adenoma. Conversely, the lack of detectable circulating markers in patients with NFPA and the scant possibility to perform a successful medical treatment in these patients project ¹²³I-IBZM scintigraphy as a useful predictive test to select patients with radiologically documented remnant tumor or patients with high surgical risk. It should be considered that ¹²³I-IBZM scintigraphy can in vivo differentiate between pituitary adenomas and other tumor masses of the pituitary region, such as meningiomas and craniopharingiomas (27), thus avoiding the risk of treating tumors that do not express D₂ receptors. The availability of ¹²³I-epidepride, a new D₂ receptor-targeting agent that displays a higher affinity for striatal uptake than ¹²³I-IBZM (28), and the possibility to use double- and triple-headed cameras, which improve the quality of images, could even ameliorate the possibility to predict the response to long-term quinagolide treatment in NFPA-bearing patients (29, 30).

Received January 21, 1997.

Revised June 27, 1997.

Revised September 23, 1997.

Accepted October 1, 1997.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Bevan JS, Webster J, Burke CW, Scanlon MF. 1992 Dopamine agonists and pituitary tumor shrinkage. Endocr Rev. 13:220–240.[CrossRef][Medline]
2. Melmed S, Ho K, Klibanski A, Reichlin S, Thorner M. 1995 Recent advances in pathology, diagnosis and management of acromegaly. J Clin Endocrinol Metab. 80:3395–3402.[CrossRef][Medline]
3. Colao A, Ferone D, Marzullo P, et al. 1997 Effect of different dopaminergic agents in the treatment of acromegaly. J Clin Endocrinol Metab. 82:518–523.[Abstract/Free Full Text]
4. Yamada S, Asa SL, Kovaks K, Muller P, Smyth HS. 1989 Analysis of hormone secretion by clinically nonfunctioning human pituitary adenomas using the reverse hemolytic plaque assay. J Clin Endocrinol Metab. 68:73–80.[Abstract]
5. Saccomanno K, Gil-del-Alamo P, Bassetti M, Reza-Elahi F, Spada A. 1993 In vitro detection of glycoprotein production and secretion by human nonfunctioning pituitary adenomas. J Endocrinol Invest. 16:109–115.[Medline]
6. Closse A, Cramps M, Wanner A, Palacios JM. 1988 In vivo labelling of brain dopamine D₂ receptors using the high-affinity specific D₂ agonist (³H)CV 205–502. Brain Res. 440:123–128.[CrossRef][Medline]
7. Brue T, Pellegrini I, Gunz G, et al. 1992 Effects of dopamine agonist CV 205–502 in human prolactinomas resistant to bromocriptine. J Clin Endocrinol Metab. 74:577–584.[Abstract]
8. Colao A, Merola B, Sarnacchiaro F, et al. 1995 Comparison among different dopamine-agonists of new formulation in the clinical management of macroprolactinomas. Horm Res. 44:222–228.[Medline]
9. Chiodini PG, Attanasio R, Cozzi R, et al. 1993 CV 205–502 in acromegaly. Acta Endocrinol (Copenh) 128:389–393.
10. Lombardi G, Colao A, Ferone D, et al. 1995 CV 205–502 treatment in therapy-resistant acromegalic patients. Eur J Endocrinol. 132:559–564.[Abstract/Free Full Text]
11. Kwekkeboom DJ, Lamberts SWJ. 1992 Long-term treatment with dopamine agonist CV 205–502 of patients with clinically non-functioning, gonadotroph, or -subunit secreting pituitary adenoma. Clin Endocrinol (Oxf). 36:171–176.[Medline]
12. Brücke T, Wenger S, Asenbaum S, et al. 1993 Dopamine D₂ receptor imaging and measurements with SPECT. Adv Neurol. 60:494–500.[Medline]
13. de Herder WW, Reijs AEM, Kwekkeboom DJ, et al. 1996 In vivo imaging of pituitary tumors using a radiolabeled dopamine D₂ receptor radioligand. Clin Endocrinol (Oxf). 45:755–767.[CrossRef][Medline]
14. Colao A, Ferone D, Lastoria S, et al. 1996 Prediction of efficacy of octreotide therapy in patients with acromegaly. J Clin Endocrinol Metab. 81:2356–2362.[Abstract]
15. Scillitani A, Dicembrino F, Di Fazio P, et al. 1995 In vivo visualization of pituitary dopaminergic receptors by iodine-123 methoxybenzamide (IBZM) correlates with sensitivity to dopamine agonists in two patients with macroprolactinomas. J Clin Endocrinol Metab. 80:2523–2525.[Abstract]
16. Verhoeff NP, Bemelman FJ, Wiersinga WM, van Royen EA. 1993 Imaging of dopamine D₂ and somatostatin receptors in vivo using single-photon emission tomography in a patient with TSH/PRL-producing pituitary macroadenoma. Eur J Nucl Med. 20:555–561.[Medline]
17. Verhoeff NP, van Royen EA, van Royen N, et al. 1991 Dopamine D₂-receptor imaging with dynamic I-123 iodo benzamide SPECT in healthy human volunteers. J Nucl Med. 32:1076–1079.
18. Ebersold MJ, Quast LM, Laws ER, et al. 1986 Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg. 334:246–254.
19. Harris PE, Afshar F, Coates P, et al. 1989 The effects of transsphenoidal surgery on endocrine function and visual fields in patients with functionless pituitary adenomas. Q J Med New Series. 71:417.
20. Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton MI. 1989 Hypopituitarism following external radiotherapy for pituitary tumors in adults. Q J Med New Series. 70:145.
21. Warnet A, Timsit J, Chanson P, et al. 1989 The effect of somatostatin analogue on chiasmal dysfunction from pituitary macroadenomas. J Neurosurg. 71:687–690.[Medline]
22. de Bruin TWA, Kwekkeboom DJ, van’t Verlaat JW, et al. 1992 Clinically nonfunctioning pituitary adenoma and octreotide response to long term high dose treatment, and studies in vitro. J Clin Endocrinol Metab. 75:1310–1317.[Abstract]
23. Merola B, Colao A, Ferone D, et al. 1993 Effects of chronic treatment with octreotide in patients with functionless pituitary adenomas. Horm Res. 40:149–155.[Medline]
24. Plöckinger U, Reichel M, Fett U, Saeger W, Quabbe HJ. 1994 Preoperative octreotide treatment of growth hormone-secreting and clinically nonfunctioning pituitary macroadenomas: effect on tumor volume and lack of correlation with immunohistochemistry and somatostatin receptor scintigraphy. J Clin Endocrinol Metab. 79:1416–1423.[Abstract]
25. Bevan JS, Burke CW. 1986 Non-functioning pituitary adenomas do not regress during bromocriptine therapy but possess membrane-bound dopamine receptors which bind bromocriptine. Clin Endocrinol (Oxf). 25:561–572.[Medline]
26. Koga M, Nakao H, Arao M, et al. 1987 Demonstration of specific dopamine receptors on human pituitary adenomas. Acta Endocrinol (Copenh). 114:595–602.[Abstract/Free Full Text]
27. de Herder WW, Lamberts SWJ. 1995 Imaging of pituitary tumours. Baillieres Clin Endocrinol Metab. 9:367–389.[CrossRef][Medline]
28. Leslie WD, Abrams DN, Greenberg CR, Hobson D. 1996 Comparison of iodine-123-epidepride and iodine-123-IBZM for dopamine D₂ receptor imaging. J Nucl Med. 37:1589–1591.[Abstract/Free Full Text]
29. Pirker W, Riedl M, Luger A, et al. 1996 Dopamine D2 receptor imaging in pituitary adenomas using iodine-123-epidepride and SPECT. J Nucl Med. 37:1931–1937.[Abstract/Free Full Text]
30. Pirker W, Brücke T, Riedl M, et al. 1994 iodine-123-IBZM-SPECT: studies in 15 patients with pituitary tumors. J Neural Transm. 97:235–244.[CrossRef][Medline]

This article has been cited by other articles:

				A. Colao, C. Di Somma, R. Pivonello, A. Faggiano, G. Lombardi, and S. Savastano Medical therapy for clinically non-functioning pituitary adenomas Endocr. Relat. Cancer, December 1, 2008; 15(4): 905 - 915. [Abstract] [Full Text] [PDF]

				D. Ferone, R. Pivonello, E. Resmini, M. Boschetti, A. Rebora, M. Albertelli, V. Albanese, A. Colao, M. D Culler, and F. Minuto Preclinical and clinical experiences with the role of dopamine receptors in the treatment of pituitary adenomas Eur. J. Endocrinol., April 1, 2007; 156(suppl_1): S37 - S43. [Abstract] [Full Text] [PDF]

				W. W de Herder, A. E M Reijs, R. A Feelders, M. O van Aken, E. P Krenning, A.-J. van der Lely, and D. J Kwekkeboom Diagnostic imaging of dopamine receptors in pituitary adenomas Eur. J. Endocrinol., April 1, 2007; 156(suppl_1): S53 - S56. [Abstract] [Full Text] [PDF]

				A. Colao, M. Filippella, R. Pivonello, C. Di Somma, A. Faggiano, and G. Lombardi Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours Eur. J. Endocrinol., April 1, 2007; 156(suppl_1): S57 - S63. [Abstract] [Full Text] [PDF]

				W. W de Herder, A. E M Reijs, R. A Feelders, M. O van Aken, E. P Krenning, H. L J Tanghe, A.-J. van der Lely, and D. J Kwekkeboom Dopamine agonist therapy of clinically non-functioning pituitary macroadenomas. Is there a role for 123I-epidepride dopamine D2 receptor imaging? Eur. J. Endocrinol., November 1, 2006; 155(5): 717 - 723. [Abstract] [Full Text] [PDF]

				R. Pivonello, C. Matrone, M. Filippella, L. M. Cavallo, C. Di Somma, P. Cappabianca, A. Colao, L. Annunziato, and G. Lombardi Dopamine Receptor Expression and Function in Clinically Nonfunctioning Pituitary Tumors: Comparison with the Effectiveness of Cabergoline Treatment J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1674 - 1683. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferone, D. Articles by Lombardi, G. Search for Related Content PubMed PubMed Citation Articles by Ferone, D. Articles by Lombardi, G.