Object: During the last 10 years, 129 consecutive transsphenoidal operations for growth hormone (GH) secreting pituitary adenomas have been carried out. In the present study, 120 of the patients involved in these operations have been reviewed to evaluate the accuracy of diagnosis of adenoma, the cure rate, and to ascertain the favorable surgical effects of early surgical intervention.

Methods: A total of 120 GH secreting adenomas, including 95 patients with typical acromegaly and 25 patients with no apparent clinical features of acromegaly, were evaluated. The pituitary tumors were investigated by means of Magnetic Resonance (MR) imaging at 1.5T and 3T, composite 3T-MRI and [11C] Methionine-positron Emission Tomography (MET-PET) imaging and histological and immunohistochemical staining. The modern remission criteria (a glucose suppressed [nadir] GH level of less than 1.0 ng/ml, a random GH level of 2.5 ng/ml or less, and a normal sex and age adjusted insulin-like growth factor-1 [IGF-1] level) were used. To assess remission we examined these criteria at 1, 6 and 12 months after surgery.

Results: The diagnostic accuracy of 3T-MRI and composite MET-PET fusion 3T- MRI in localizing adenoma was 87 and 100%, respectively. The mean age of patients with pre-clinical acromegaly and acromegaly was 37.3 and 51.1 years, respectively. The mean preoperative GH levels in these patients were 4.85 and 34.7 ng/ml for preclinical acromegaly and acromegaly, respectively. The mean preoperative IGF-1 levels for pre-clinical acromegaly and acromegaly were 323 and 822 ng/ml, respectively. The mean volume of the adenoma in patients with pre-clinical acromegaly and acromegaly were 1.26 and 3.84 cm3, respectively. There was a significant difference (P <0.0001) between the pre-clinical acromegaly and acromegaly groups in terms of age, GH and IGF-1 levels, and tumor volume. The overall cure rate for growth hormone-secreting adenoma was 73% using modern criteria; the surgical cure rate for acromegaly patients was 65%, while the surgical cure rate for patients without obvious clinical features of acromegaly was 100%. Patients with pre-clinical acromegaly had a tendency to have smaller sized adenomas, a younger age, lower GH and IGF-1 levels, and a better surgical cure rate relative to patients with typical acromegaly. No complications such as carotid artery injury, hypothalamic injury, cerebrospinal fluid fistula or permanent diabetes insipidus occurred. Only one acromegaly patient had hypopituitarism after surgery.

Conclusions: Early detection of GH secreting adenoma is important since early surgical intervention can achieve a 100% cure rate without serious complications.

There are numerous pathologic causes of galactorrhea. Hyperprolactinemia and hypothyroidism are frequently associated with galactorrhea as a result of hormonal imbalances. Patients with acromegaly sometimes have hyperprolactinemia, and some also have galactorrhea. Here, we report on a male patient with acromegaly who suffered from galactorrhea without hyperprolactinemia. This 42-year-old patient had a pituitary adenoma, but his serum hormone levels were within normal ranges, except for the growth hormone and insulin-like growth factor 1. Transsphenoidal surgery was performed and subsequent histopathologic studies confirmed it was a plurihormonal adenoma. After surgery, his GH and IGF-1 levels decreased to within the normal ranges, and his galactorrhea also disappeared. To the best of our knowledge, this is the first reported case of a male patient with acromegaly who suffered from galactorrhea without hyperprolactinemia.

Aim: To disclose the nature of plurihormonality and pluripotentiality of growth hormone (GH)-secreting adenomas.
Methods: A total of 242 patients with GH-secreting adenomas were studied by immunohistochemistry, electron microscopy and clonal analysis (X-linked human androgen receptor gene assay).
Results: GH-secreting adenoma showed a greater variety and number of hormones produced compared with those of PRL-secreting adenomas (p<0.01, Welch’s t-test). The number of cases with GH-secreting adenoma that simultaneously produced ACTH were 50 (21%) out of 242. There were two different types of co-localization of ACTH- and GH-secreting cells within adenoma; (1) adenoma with co-localized ACTH- and GH-immunoreactive cells in a random pattern, and (2) adenoma with a small cell cluster of ACTH-immunoreactive cells within GH-secreting adenomas. There were three different tissue phenotypes in GH-secreting adenomas; (a) mixed tumors composed of adenoma and neuronal cells, (b) co-localization of GHsecreting adenoma and mature bone tissue, and (c) co-localization of GH-secreting adenoma and nerve bundles. In this study, immunoreactivity for nestin was observed in these three different phenotypes of GH-secreting adenomas, not only in perivascular spaces of pituitary tumor vessels but also in parenchymal cells of the pituitary adenoma.
Conclusion: Various kinds of cells can differentiate from the stem cells in GH-secreting adenomas, which may result in plurihormonality and pluripotentiality of adenomas.

Background: Normalization of abnormal Growth Hormone (GH) and Insulin-like Growth Factor (IGF)-1 secretion is essential for the treatment of acromegaly. Although the diagnostic accuracy of magnetic resonance imaging (MRI) has increased in recent years, MRI may fail to detect residual adenoma, even in patients with high IGF-1 levels. The recently developed composite methionine (MET)-PET fusion 3 Tesla (3T)-MRI technique has helped us to determine the location of adenomas that could not be detected by conventional MRI. Regions with high MET uptake are suggestive of residual adenomas. In this study, we sought to confirm the positional relationship between regions of high MET uptake and the sites of viable residual adenoma cells.
Methods: We analyzed the results of six patients who underwent gamma knife radiosurgery or re-operation as adjuvant therapy with the aid of composite MET-PET fusion MRI.
Results: Based on our experiences in these six patients, composite MET-PET fusion 3T-MRI is useful to plan surgery, and to plan the dose and area of radiation required for gamma knife radiosurgery of an active lesion.
Conclusion: The use of composite MET-PET fusion 3T-MRI and subsequent dose planning enabled us to achieve a high remission rate with adjuvant therapy for patients with acromegaly, because MET-PET could clearly detect and delineate the residual tumor.

Objective: To evaluate the usefulness of methionine (MET)-Positron Emission Tomography (PET) for the early diagnosis of Growth Hormone (GH) secreting adenomas, we retrospectively analyzed patients with abnormal GH dynamics and a histologically confirmed GH secreting pituitary adenoma who underwent pre-operative fluorodeoxyglucose-/MET-PET.

Materials and methods: Thirty-two patients with abnormal GH dynamics were included in this study. 3 Tesla (3T) -MRI, [18F]-flurodeoxyglucose (FDG) -/[11C]-MET-PET, and transsphenoidal surgery were performed in all the patients. We determined correlations among FDG-/MET-PET (maximum standardized uptake value (SUVmax)), serum GH and IGF-1 levels, the GH response to a 75 g Oral Glucose Tolerance Test (OGTT), Thyrotropin-Releasing Hormone (TRH) /Luteinizing Hormone-Releasing Hormone (LHRH) loading tests, tumor volume, and proliferative activity.

Results: The diagnostic sensitivity for early GH secreting adenoma was highest for MET-PET (100%), followed by TRH/LHRH (80%), 75 g OGTT (67%), and FDG-PET (47%). Significant correlations were observed between: MET-PET SUVmax and FDG-PET SUVmax (p<0.01), MET-/FDG-PET SUVmax and tumor volume (MET: p<0.01; FDG: p<0.01) ; MET-/FDG PET SUVmax and MIB-1 labeling index (MET: p<0.01; FDG: p=0.01) ; GH/insulin-like growth factor (IGF)-1 levels and tumor volume (GH: p=0.01; IGF-1: p<0.01) ; and GH and IGF-1 levels (p<0.01).

Conclusions: All the patients with abnormal GH dynamics detected by MET-PET had GH adenomas, indicating that MET-PET is useful for the early diagnosis of GH adenomas.