The British Journal of Radiology, 78 (2005), 110–115 E 2005 The British Institute of Radiology
The role of somatostatin receptor scintigraphy in patients
with pituitary adenoma or post-surgical recurrent tumours
M J ACOSTA-GOMEZ, MD, 1M A MUROS, MD, PhD, 1J M LLAMAS-ELVIRA, MD, PhD,
A RAMıREZ, MD, PhD, 1S ORTEGA, MD, 1G SABATEL, MD, 1C RAMOS, MD and 2A DE LA RIVA-
AGUILAR, MD, PhD
Department of Nuclear Medicine, Virgen de las Nieves Hospital, Avda. de las Fuerzas Armadas 2, 18014 Granada and
Department of Neurosurgery, University Hospital ‘‘Reina Sofıa’’, Cordoba, Spain
Abstract. To assess the role of scintigraphy with 111In-DTPA-D-Phe-octreotide (111In-octreotide) in the
diagnosis of pituitary adenomas and in the evaluation of post-surgical recurrent or residual tumours, we
performed scintigraphy with 111In-DTPA-D-Phe-octreotide (SRS) in 35 patients: 14 patients with conﬁrmed
pituitary tumours and 15 with conﬁrmed recurrent tumours. Clinical, biochemical and histological analyses,
conventional images (CT/MRI), and follow-up assessments during a period of 1 year to 4 years were recorded in
all patients. In the present study, scintigraphy with 111In-octreotide showed positive uptake in 10 out of 14
patients with conﬁrmed pituitary tumour and in 13 out of 15 patients with conﬁrmed recurrent tumour, with an
overall sensitivity of 79%. SRS showed better results in growth hormone (GH)- and prolactin (PRL)-secreting
tumours (7/8 patients correctly identiﬁed) than in other adenomas (3/9). SRS detected recurrence of
adenocorticotrophic hormone (ACTH)-secreting tumours (4/5 patients correctly identiﬁed) and non-secreting
tumours (5/7 patients correctly identiﬁed). 111In-octreotide scintigraphy, in combination with other imaging
modalities, is useful in the diagnosis and follow-up of pituitary tumours. It allows scar tissue to be differentiated
from tumour recurrence after surgical treatment and ensures better selection of patients who will beneﬁt from
medical treatment with somatostatin analogues.
The in vivo visualization of somatostatin receptors is chiasm. MRI signal characteristics do not necessarily
becoming more widely used to diagnose neuroendocrine assess the consistency of the tumour accurately but the
tumours and to assess the therapeutic effects of somato- superior and inferior extent of tumour is well demon-
statin analogues in these patients . Somatostatin strated by MRI.
receptors have been demonstrated in vitro in most cases It is not easy to distinguish between recurrent/residual
of growth hormone (GH)-secreting adenomas and in some tumour and scar/necrotic tissue after surgery . The
cases of thyroid stimulating hormone (TSH)-secreting scintigraphic visualization of hypophyseal tumours may be
adenomas and prolactinomas. Controversial results have of value for predicting the response to somatostatin
been reported in other types of pituitary adenomas, such analogue treatment and for the post-surgical detection of
as non-secreting adenomas [2–5]. GH-secreting tumours small or residual tumours that are undetectable on MRI.
express somatostatin receptor subtypes 2, 3 and 5, whereas Although some authors have reported that somatostatin
non-secreting adenomas mainly express subtype 3 . receptor scintigraphy (SRS) did not permit visualization of
In the diagnostic work-up of patients with pituitary post-surgical tumours that were not visible on MRI ,
adenomas, CT and MRI play a principal role in deﬁning other authors have described its utility to detect minimal
the localization and tumour size, as in all brain tumours, post-surgical residual tumours .
but histological diagnosis can only be performed post- The present study aimed to assess the utility of SRS in
operatively. MRI is now the investigation of choice in the diagnosis of pituitary adenomas and in the evaluation
diagnosis of pituitary adenomas. Micro-adenomas are of post-surgical recurrent or residual tumours.
deﬁned as being smaller than 10 mm in size and usually
present because of endocrine dysfunction (the most
common is prolactinoma). 80–85% of micro-adenomas Patients and methods
are visible on unenhanced T1 weighted MR images and
33–50% are seen as areas of hyperintensity on T2 weighted Patients
images, and enhancement with dynamic scanning is only
We performed a prospective study of 35 patients
necessary in a minority of cases. Macro-adenomas are
referred to our Department of Nuclear Medicine for
more likely to be non-functioning and present because of
suspicion of pituitary tumour or suspicion of pituitary
mass effect on adjacent structures such as the optic
tumour recurrence over 5 years (1997–2001). 35 patients
Received 6 April 2004 and in revised form 23 August 2004, accepted 27 (23 females, 12 males) aged between 9 years and 77 years
September 2004. (mean age 43 years) were referred by the Departments of
Address correspondence to Dr Maria Angustias Muros, Servicio de
Neurosurgery, Endocrinology and Radiotherapy. All
Medicina Nuclear, Hospital Virgen de las Nieves, Avda. Fuerzas patients gave their informed consent to undergo the
Armadas, 2, 18014 Granada, Spain. scintigraphy. The Ministry of Health approved the
110 The British Journal of Radiology, February 2005
Somatostatin receptor scintigraphy in pituitary adenomas
compassionate use of the radiopharmaceutical in all cases. N Grade II: moderate tracer uptake with good visualiza-
18 of the patients were referred for suspected tumour tion of tumour; uptake slightly greater than that in
recurrence due to the persistence or post-surgical onset of skull;
clinical symptoms (n59) or elevated levels of hormone N Grade III: intense tracer uptake; uptake clearly greater
markers (n59). Tumour types in these patients included: than that in skull.
adenocorticotrophic hormone (ACTH)-secreting (n55),
GH-secreting (n53), prolactin (PRL)-secreting (n52),
follicle stimulating hormone (FSH)-secreting adenomas MRI
(n51) and non-secreting adenomas (n57). The remaining
17 patients were referred for suspicion of pituitary MRI was performed using a 0.5-T scanner (GE Max
adenomas, presenting with PRL-secreting (n54), GH- Medical System, Milwaukee, WI). T1 weighted gradient
secreting (n54), ACTH-secreting (n53) adenomas, non- echo imaging (without contrast) was performed with a
secreting adenomas (n53), and thyroid stimulating repetition time (TR) of 380 ms and echo time (TE) of
hormone (TSH)- (n51), FSH- (n51), and leutinizing 12 ms. T2 weighted and proton density variable echo (VE)
hormone (LH)- (n51) secreting adenomas. None of 18 imaging was performed with a TR of 2600 ms, TE of 40–
patients referred for suspected tumour recurrence were 120 ms, and T1 weighted spin-echo (SE) with a TR of
included in the primary tumours group. 600 ms, and TE of 25 ms. Studies were also performed
Clinical data and biochemical determinations were with paramagnetic contrast: T1 weighted SE imaging,
recorded for all patients prior to the scintigraphic using sections of 3 mm thickness with 4 mm section
examination. The analytical ﬁndings included levels of interval. Images were obtained in the coronal and axial
GH, somatomedin C, insulin-like growth factor-1 (IGF1) planes.
growth factor, prolactin, TSH, ACTH, FSH, and LH, and
the results of stimulation and inhibition tests of these
hormones. CT or MRI and ophthalmological (visual ﬁeld) CT
studies were carried out in all cases. The mean follow-up CT scan was carried out before and after intravenous
period was 2.5 years (range 1–4 years). infusion of contrast medium using a third generation
A tailored therapeutic approach was developed for Siemens Somatom CR scanner. Section thickness was 4 mm.
each patient, using somatostatin analogues, radio-
surgery, medical treatment or surgery as appropriate.
Five patients (three with pituitary adenomas and two with Analytical studies: hormone determinations
tumour recurrence) underwent surgery and the path-
ological report conﬁrmed the presence of pituitary The following hypophyseal hormones were determined
adenoma or tumour recurrence. The diagnosis was in all patients: GH, ACTH, PRL, TSH, FSH, and LH.
conﬁrmed in the remainder by imaging tests (CT or IGF1 growth factor was also measured. The determina-
MRI) in conjunction with analytical results and clinical tions were made by radioimmunoanalytical techniques for
ﬁndings. FSH, LH and PRL (Diagnostic System Laboratories, Inc.,
TX), GH (IRMA, Immunotech, France), TSH (IRMA,
Immunodiagnostic Systems Ltd., UK), and ACTH
(Nichols Institute, CA, USA). Hormone inhibition and
[111In-DTPA-D-Phe]-octreotide scintigraphy stimulation tests were carried out: inhibition test with
The scintigraphy was performed with 185–220 MBq dexamethasone for ACTH-secreting tumours and oral
(5–6 mCi) of 111In-chloride-DTPA-D-Phe-octreotide glucose overload test for GH-secreting tumours.
(Octreoscan) obtained from a simple Mallinckrodt kit
(Mallinckrodt Iberica S.A. Spain), which was intrave-
nously administered to all patients. No post-administra- Follow-up
tion adverse reactions or side effects were detected in any All patients were followed up every 6 months, provided
patient. Image acquisition was with single-head (Siemens no clinical situations occurred requiring more urgent
Orbiter; Gammasonics, IL) and double-head (AXIS2; assessment or admission. The follow-up consisted of:
Picker International, Nuclear Medicine Division, MRI examinations, which were always compared with
Cleveland, OH) gamma cameras with medium energy previous images, hormonal analytical determinations, and
collimator. Planar images were obtained 4 h, 24 h and clinical examinations.
48 h post-injection in all patients, with at least 500 000 Complete remission was deﬁned as normalization of all
counts/acquired per image or 10 min image21. clinical sings with normal tumour markers (including basal
Tomographic images (SPECT) were obtained 4 h and and dynamic responses of hypophyseal hormones) at 1
24 h post-injection, if using the double-head camera, year after therapy with no evidence of residual tumour on
through a 360 ˚ orbit, acquiring 60 steps at 40 s step21, CT or MRI. The patient was considered to have tumour
using a 64664 matrix. The image analysis was performed recurrence if clinical, biochemical and/or neuroradiological
by two nuclear medicine specialists according to a signs of tumour activity were detected after therapy.
qualitative evaluation system visually comparing the
tracer uptake in the suspected tumour with that in the
skull [10–12]. The grades were deﬁned as follows: Results
N Grade 0: absence of tracer uptake, no visualization of Among the 17 patients referred for suspicion of pituitary
tumour activity, considered negative; tumour, SRS was positive in 10 patients (Table 1,
N Grade I: slight tracer uptake, similar to that in skull; Figure 1). The MRI was positive in all 10 patients. Two
The British Journal of Radiology, February 2005 111
M J Acosta-Gomez, M A Muros, J M Llamas-Elvira et al
Table 1. Data of patients with suspected pituitary adenoma
N˚ Sex/age Tumour type SRS MRI Size (cm) Treatment Follow up
1 F/55 PRL-secreting Positive-III Positive 3.3 Somatostatin analogues Size reduction, clinical
2 M/52 PRL-secreting Positive-III Positive 6 Somatostatin analogues Complete remission (TP)
3 F/14 PRL-secreting Positive-II Positive 2.5 Radiosurgery Size reduction (TP)
4 M/64 PRL-secreting Negative Positive 1.6 Radiosurgery Size reduction (FN)
5 F/67 GH-secreting Positive-I Positive 0.8 Somatostatin analogues Size reduction (TP)
6 F/42 GH-secreting Positive-II Positive 1.2 Somatostatin analogues Size reduction, clinical
7 M/40 GH-secreting Positive-I Positive 0.3 Radiosurgery Complete remission (TP)
8 F/44 GH-secreting Positive-III Positive 2.5 Surgery Complete remission (TP)
9 M/57 Non-secreting Positive-II Positive 2.5 Surgery Complete remission (TP)
10 F/67 Non-secreting Negative Positive 2.7 Medical Clinical improvement (FN)
11 F/66 Non-secreting Negative Positive 2 None Stable (FN)
12 F/65 ACTH-secreting Negative Positive 0.9 Surgery Complete remission (FN)
13 F/76 ACTH-secreting Negative Negative no mass None Without symptom, MRI (-) (TN)
14 F/42 ACTH-secreting Negative Negative no mass None Without symptom, MRI (-) (TN)
15 F/14 FSH-secreting Negative Positive (FP) 1 None Without symptom, MRI (-) (TN)
16 F/9 LH-secreting Positive-II Positive 0.2 Medical Clinical improvement (TP)
17 M/68 TSH-secreting Positive-III Positive 2.5 Somatostatin analogues Clinical improvement (TP)
SRS, somatostatin receptor scintigraphy; PRL, prolactin; GH, growth hormone; ACTH, adenocorticotrophic hormone; FSH, follicle
stimulating hormone; LH, leutinizing hormone; TSH, thyroid stimulating hormone; TP, true positive; TN, true negative; FN, false
negative; FN, false positive.
of these 10 patients underwent surgery and the patholo- II or III and two patients with Grade I. Each patient with
gical report conﬁrmed the presence of pituitary adenoma; Grade I had GH-secreting adenoma less than 1 cm in size.
six patients were treated with somatostatin analogues, and SRS was negative in seven patients. In three of these, the
the remaining two patients (with smaller tumour size) absence of the disease was conﬁrmed by conventional
received radiosurgery or medical treatment. In follow-up imaging studies, biochemical ﬁndings, and clinical follow-
studies, all 10 patients showed clinical, biochemical and/or up. The initial MRI examination was positive in one case
radiographic improvements after therapy. According to (N˚ 15), but subsequent biochemical and clinical follow-up
their tracer uptake, eight patients were scored with Grades ruled out the presence of adenoma in this patient.
Figure 1. (a) Anterior and (b) lateral images of 111In-chloride-DTPA-D-Phe-octreotide accumulation in the tumour site in a patient
(N˚ 17) with thyroid stimulating hormone (TSH)-secreting adenoma. The images were taken in a Siemens single-head gamma camera
24 h after tracer administration.
112 The British Journal of Radiology, February 2005
Somatostatin receptor scintigraphy in pituitary adenomas
Table 2. Data of patients with suspected recurrent pituitary adenoma
N˚ Sex/age Tumour type SRS MRI Size (cm) Treatment Follow up
18 M/32 ACTH-secreting Positive-III Positive small nodule Somatostatin Complete remission (TP)
19 F/51 ACTH-secreting Positive-II Negative 2.5 Radiosurgery and Complete remission (TP)
20 F/66 ACTH-secreting Positive-I Positive 2.5 Radiosurgery Size reduction (TP)
21 F/37 ACTH-secreting Positive-II Positive small nodule Medical Size reduction (TP)
22 F/34 ACTH-secreting Negative Positive small nodule Medical Without symptom, MRI (-) (TN)
23 M/56 Non-secreting Positive-II Positive scant remains Somatostatin analogues Clinical improvement (TP)
24 M/54 Non-secreting Positive-II Positive 3.8 Somatostatin analogues Clinical improvement (TP)
25 M/36 Non-secreting Positive-I Negative no mass Medical Clinical improvement, MRI (+) (TP)
26 M/66 Non-secreting Negative Negative no mass None Without symptom, MRI (-) (TN)
27 M/56 Non-secreting Positive-I Positive 2.9 None Stable (TP)
28 F/40 Non-secreting Positive-I Positive 2 Somatostatin Clinical improvement (TP)
29 F/46 Non-secreting Negative Positive 1.6 Radiosurgery Clinical improvement (FN)
30 F/50 GH-secreting Positive-II Positive 2 Somatostatin analogue Complete remission (TP)
31 F/45 GH-secreting Negative Negative no mass None Without symptom, MRI (-) (TN)
32 F/33 GH-secreting Negative Positive 1 Radiotherapy Clinical improvement (FN)
33 F/77 PRL-secreting Positive-II Positive 5 Surgery Clinical improvement (TP)
34 M/47 PRL-secreting Positive-I Positive 2 Medical Complete remission (TP)
35 F/32 FSH-secreting Positive-III Positive 4.6 Somatostatin analogues Size reduction (TP)
ACTH, adenocorticotrophic hormone; GH, growth hormone; PRL, prolactin; FSH, follicle stimulating hormone; SRS, somatostatin
receptor scintigraphy; TP, true positive; TN, true negative; FN, false negative; FN, false positive.
Scintigraphy failed to detect the presence of tumour in Among the 18 patients examined for recurrent/residual
four patients: two with non-secreting adenomas, one with pituitary tumour, SRS was positive in 13 patients
an ACTH-secreting adenoma of less than 1 cm, and one (Table 2). Of these, one (with largest tumour size)
with a prolactinoma. underwent repeat surgery, ﬁve (with highest uptake
SRS showed better results in GH- and PRL-secreting grades, II and III) were treated with somatostatin
tumours (7/8 patients correctly identiﬁed) than in other analogues, two with radiosurgery, three underwent
adenomas (3/9). medical treatment and one patient was treated with
Figure 2. (a) MRI in the patient N˚ 21. Represent a study in a coronal view showing a small recurrent tumour in contact with right
optic nerve. (b) Lateral images of 111In-chloride-DTPA-D-Phe-octreotide accumulation in the recurrent tumour site in a patient (N˚
21) with recurrent adenocorticotrophic hormone (ACTH)-secreting adenoma. The images were taken in a Siemens single-head gamma
camera 24 h after tracer administration.
The British Journal of Radiology, February 2005 113
M J Acosta-Gomez, M A Muros, J M Llamas-Elvira et al
radiotherapy and somatostatin analogues. The remaining suspicion of FSH- and LH-secreting tumours were
patient (N˚ 27) refused treatment. In all 13 patients, the correctly diagnosed using SRS. The utility of SRS was
recurrence was conﬁrmed by clinical and biochemical data less for non-secreting adenomas in our study, with uptake
and MRI results. In two of the patients (N˚ 19 and 25) in one out of the three patients who showed grade II
with positive SRS, the MRI gave a negative result uptake and underwent surgical treatment. Oppizzi et al
(Figure 2), and the recurrence was demonstrated by  found uptake in 14 out of 22 patients and Schmidt et al
clinical and biochemical results in follow-up. SRS was  detected uptake in six out of 14 such patients. On the
negative in ﬁve patients: the absence of recurrence was other hand, Duet et al  found uptake in ﬁve out of ﬁve
demonstrated by imaging tests and follow-up in three patients with non-secreting adenoma. We studied one
cases, whereas in the remaining two patients, recurrence patient diagnosed with ACTH-secreting adenoma and
was conﬁrmed by imaging (MRI and CT) and the detected no uptake, in keeping with several other studies.
evaluation of post-treatment improvements. MRI was De Herder and coworkers detected no uptake in eight
negative for recurrence in four patients. The absence of patients with ACTH-secreting adenoma and Stalla et al
recurrence was conﬁrmed in two of them (N˚ 26 and 31). suggested that the elevated cortisol levels in patients with
SRS correctly diagnosed 16 of the 18 patients with sus- ACTH-secreting adenoma may inhibit the expression of
pected recurrence, whereas MRI correctly diagnosed 14 of somatostatin receptors [20–22].
the 17 patients who had MRI (one patient refused MRI). Among the patients with conﬁrmed tumour recurrence,
According to our results, SRS showed the best results in ¨
SRS correctly detected 13 out of 15 patients. Plokinger et al
cases of recurrence of ACTH-secreting tumours (4/5  studied 10 patients after surgery for GH-secreting
patients correctly identiﬁed) and non-secreting tumours pituitary adenoma. Seven of them with tumours associated
(5/7 patients correctly identiﬁed). with persistent elevation of GH levels were not detected by
In the present study, scintigraphy with 111In-octreotide scintigraphy. They concluded that SRS is not useful in
showed uptake in 10 out of 14 patients with conﬁrmed detecting tumour recurrence in cases with a negative MRI
pituitary tumour and in 13 out of 15 patients with result. In our study, tumour recurrence was diagnosed by
conﬁrmed recurrence, with an overall sensitivity of 79%. SRS in 13 patients and two of them had a negative MRI.
The diagnosis of recurrence was subsequently conﬁrmed in
all cases. Lauriero et al  showed uptake in eight of 10
Discussion patients (4 GH-secreting and 6 PRL-secreting adenomas)
The presence of high-afﬁnity somatostatin receptors in diagnosed with tumour recurrence. Both patients in our
most neuroendocrine tumour cells allows the in vivo study with suspected recurrence of PRL-secreting tumour
scintigraphic visualization of neuroendocrine tumours showed positive uptake. Out of seven patients in our study
after the intravenous administration of a radiolabelled with recurrence of non-secreting adenoma, ﬁve had
somatostatin analogue. The diagnosis of suspected cases of positive uptake of octretide, with no false positive cases.
pituitary tumour or pituitary tumour recurrence can be In the present study, scintigraphy showed good results
based on CT and MRI but the deﬁnitive diagnosis depends in patients with suspected recurrence of ACTH-secreting
on histopathological study following surgery. When pituitary adenoma, with detection in four out of the ﬁve
tumour recurrence is suspected, it can be difﬁcult to patients. Various authors have studied the presence of
distinguish between residual tumour and scarring asso- somatostatin receptors in pituitary adenomas and the
ciated with post-surgical changes using CT or MRI . inhibitory effects of somatostatin, including on ACTH-
Scintigraphy with 111In-octreotide allows the visualization secreting adenomas, with very variable results . Spada
of pituitary tumours on the basis of fundamental et al  studied the inhibitory effects of somatostatin
characteristics of membrane receptors. Initially, these in vivo in six patients with ACTH-secreting pituitary
studies used 123I-Tyr3-octreotide to radiolabel somato- adenoma who underwent transesphenoidal surgery, and all
statin analogues [1, 13–15]. Subsequently, the use of 111In- showed positive results, implying that these tumours must
DTPA-D-Phe-Octreotide became widespread and iodine have somatostatin receptors. In contrast, no uptake was
labelling was abandoned. In the present study, scintigra- shown by receptor scintigraphy in any of the 19 patients
phy with 111In-octreotide showed positive uptake in 10 with Cushing’s disease or eight patients with ACTH-
out of 14 patients with conﬁrmed pituitary tumour and 13 secreting pituitary adenoma in a prospective in vivo study
out of 15 patients with conﬁrmed recurrence, with an by De Herder et al, although uptake was present in eight
overall sensitivity of 79%. Reports on the sensitivity of this out of 10 patients with ectopic secretion of ACTH .
technique have been variable, ranging from 37% found by This discrepancy may be due to the long-term exposure of
Schmidt et al , who studied 24 patients and obtained patients with ACTH-secreting adenoma to excessive levels
positive uptake in only nine (9/24), to 88.5% described by of circulating cortisol. This exposure could negatively
Colao et al  in a study of 38 patients with pituitary inﬂuence the expression of somatostatin receptors ,
adenomas. In our study, the best results were for GH- and whose presence in these tumours has been conﬁrmed by in
PRL-secreting tumours (7/8), similar to the ﬁndings of vitro studies [6, 22, 24]. The present study demonstrates
Legovini et al  and Oppizzi et al . Among our ﬁve there may be a use for SRS in patients with suspected
patients with pituitary tumour that did not secrete GH or recurrence of ACTH-secreting pituitary adenoma,
PRL, three showed tracer uptake (1 TSH-secreting although the sample size was small.
adenoma, 1 LH-secreting adenoma and 1 non-secreting
adenoma). Van Royen et al  showed uptake in ﬁve out
of six patients with non-GH-secreting pituitary adenoma
(2 non-functioning, 2 TSH-secreting, 1 prolactinoma and 1 SRS, in combination with other imaging modalities, is a
Nelson’s syndrome). In our study, two patients with useful tool in the diagnosis and follow-up of pituitary
114 The British Journal of Radiology, February 2005
Somatostatin receptor scintigraphy in pituitary adenomas
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