Prolactin-secreting Tumors Research Articles

Comparative efficacy and safety of generic (Bergolak) vs. brand cabergoline in the treatment of patients with prolactin-secreting tumors

Objective: To evaluate the effectiveness and safety of cabergoline drug Bergolak («Veropharm», Russia) in the treatment of patients with prolactin-secreting tumors.Materials and methods: The study included 14 patients (14 women, mean age 46±12) diagnosed with prolactinoma. The patients were switched to Bergolak after 1 month of treatment by original cabergoline. Dose of cabergoline varied from 0,125 mg to 3,25 mg per week. Prolactin level, symptoms of hyperprolactinemic hypogonadism, side-effects were evaluated at the baseline, after 1 month of original cabergoline treatment and 1 and 2 months of Bergolak therapy.Results: Statistical differences in the level of prolactin (p 0.05), and the incidence of side-effects (p 0.43) during Bergolak therapy in comparison with the original drug was not registered.Conclusions: Bergolak showed to be effective drug for treatment of patients with prolactin-secreting tumors. The incidence of side-effects during Bergolak therapy is equal to the original cabergoline treatment.

Evaluation of survivin splice variants in pituitary tumors.

PurposeSurvivin is an apoptosis inhibitor, expressed in almost all types of human malignancies, but rarely in differentiated normal tissues. Recently, survivin gene splice variants with different anti-apoptotic activities have been reported. The current study was undertaken to examine the expression of survivin and its splice variants ∆Ex3 and 2β in pituitary tumors, and to correlate the amount of particular transcripts with clinical staging in pituitary adenomas. Quantitative detection of survivin and its splice variants ∆Ex3 and 2β transcripts in non-cancerous pituitary tissues (n = 12) and different types of pituitary tumor (n = 50).MethodsSamples were collected from 50 pituitary tumors including 26 non-functional tumors, 21 GH-secreting tumors, 2 PRL-secreting tumors and 1 ACTH-secreting tumor. 12 normal pituitary glands received after autopsy served as a control of the study. 29 thyroid cancers tissues were used as a positive control. The RT-qPCR with TaqMan hydrolysis probes were used to determine the expression of analyzed splice variants of survivin.ResultsThe obtained data showed that both survivin and its splice variants were expressed in different types of pituitary adenoma as well as in normal pituitary tissue. However, the level of its expression was similar in all studied cases. Patient age negatively correlated with tumor invasiveness. Moreover, our study showed a tendency for negative correlation between patient age and tumor diameter.ConclusionsNo significant differences between survivin and its splice variants ∆Ex3 and 2β expression in pituitary tumors and in normal pituitary glands as well as in invasive and in non-invasive tumors were found, suggesting that survivin does not play a significant role in pituitary tumorigenesis.

Hypopituitarism patterns and prevalence among men with macroprolactinomas

Men with prolactin-secreting tumors usually harbor macroadenomas. The degree of pituitary dysfunction may vary among different adenoma size subgroups, as is recovery after treatment. Our study purpose was to characterize hypopituitarism and recovery after treatment in men with macroprolactinomas. A retrospective study, including a consecutive group of 81 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (>7×ULN). Patients were divided into three categories according to adenoma size at presentation: 10-19 mm (group A), 20-39 mm (group B), and ≥40 mm (group C). We compared total testosterone, gonadotropins, cortisol, thyroid hormones and hemoglobin levels at presentation and after treatment. Eighty-one patients were included; 24, 31 and 26 patients in groups A, B and C, respectively. Pretreatment hypogonadism prevalence was 75.0, 93.5 and 90.9% (p = 0.046; A vs B and C), central hypocortisolism - 0, 6.9 and 33.3% (p = 0.005), and central hypothyroidism - 6.7, 17.9 and 26.1% (NS) in groups A, B and C, respectively. Only 26.7% of all patients presented with hypocortisolism and/or hypothyroidism (42.9% in group C). Anemia (Hb < 13.5 g%) was detected in 31.3, 57.1 and 80.0% in groups A, B and C, respectively (p = 0.04). Larger adenoma diameter correlated strongly with lower FT4 levels following treatment (r = -0.42, p = 0.043). Macroprolactinomas in men caused partial hypopituitarism, affecting testosterone in all adenoma size groups and cortisol more in patients with larger adenomas. However, most of the men did not have pituitary hormones affected, beside testosterone. Most patients recovered central hypocortisolism but not hypothyroidism following treatment.

AIP inactivation leads to pituitary tumorigenesis through defective Gαi-cAMP signaling

The aryl hydrocarbon receptor interacting protein (AIP) is a tumor-suppressor gene underlying the pituitary adenoma predisposition. Thus far, the exact molecular mechanisms by which inactivated AIP exerts its tumor-promoting action have been unclear. To better understand the role of AIP in pituitary tumorigenesis, we performed gene expression microarray analysis to examine changes between Aip wild-type and knockout mouse embryonic fibroblast (MEF) cell lines. Transcriptional analyses implied that Aip deficiency causes a dysfunction in cyclic adenosine monophosphate (cAMP) signaling, as well as impairments in signaling cascades associated with developmental and immune-inflammatory responses. In vitro experiments showed that AIP deficiency increases intracellular cAMP concentrations in both MEF and murine pituitary adenoma cell lines. Based on knockdown of various G protein α subunits, we concluded that AIP deficiency leads to elevated cAMP concentrations through defective Gαi-2 and Gαi-3 proteins that normally inhibit cAMP synthesis. Furthermore, immunostaining of Gαi-2 revealed that AIP deficiency is associated with a clear reduction in Gαi-2 protein expression levels in human and mouse growth hormone (GH)-secreting pituitary adenomas, thus indicating defective Gαi signaling in these tumors. By contrast, all prolactin-secreting tumors showed prominent Gαi-2 protein levels, irrespective of Aip mutation status. We additionally observed reduced expression of phosphorylated extracellular signal-regulated kinases 1/2 and cAMP response element-binding protein levels in mouse and human AIP-deficient somatotropinomas. This study implies for the first time that a failure to inhibit cAMP synthesis through dysfunctional Gαi signaling underlies the development of GH-secreting pituitary adenomas in AIP mutation carriers.

Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro

Background Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma. Methods In the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods. Results Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells. Conclusions There is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

Hirsutism in a Female Adolescent Induced by Long-Acting Injectable Risperidone

Hirsutism in a Female Adolescent Induced by Long-Acting Injectable Risperidone

Abstract LB-249: Reduced expression of the long non-coding RNA MEG3 in sporadic and MEN1-associated tumors.

Abstract Rapidly growing evidence shows the emerging tumor suppressor role of large non-coding RNAs (lncRNAs) in cancer pathogenesis. Maternally expressed gene 3 (MEG3) is a lncRNA that belongs to the imprinted DLK1-MEG3 locus located on human chromosome 14q32.3. Recent studies have shown reduced MEG3 expression and promoter hyper-methylation in common pituitary adenomas, classifying MEG3 as an epigenetically-regulated tumor suppressor gene. Pituitary tumor is one of the tumor types observed in the multiple endocrine neoplasia type 1 (MEN1) syndrome. MEN1 is caused by heterozygous germline mutations (1st hit) in the MEN1 tumor suppressor gene encoding menin. Subsequent tissue-specific inactivation of the normal copy of the MEN1 gene (2nd hit) leads to tumors in the parathyroids, anterior pituitary, and endocrine pancreas. Somatic MEN1 mutations are also observed in sporadic parathyroid and pancreatic endocrine tumors. We have recently demonstrated by ChIP-seq and gene expression analysis of mouse embryonic stem cells that, loss of menin results in significant loss of H3K4me3 at the Meg3 locus, and reduced expression of Meg3. These observations suggest menin-regulated epigenetic modification and expression of MEG3 as a probable mechanism for tumorigenesis. Characterization of the expression levels of MEG3 in the different tumor types associated with the MEN1 syndrome can provide valuable insights into the role of MEG3 in the pathogenesis of these tumors as well as sporadic tumors. In the current study, we used quantitative real-time PCR to evaluate the expression of MEG3 in sporadic parathyroid tumors (4 carcinoma, 8 hyperplasia, and 8 adenoma), pituitary tumors (3 sporadic ACTH-secreting, and 4 MEN1-associated: 1 ACTH secreting, 2 PRL-secreting, 1 non-functional), and sporadic pancreatic islet tumors (30 insulinomas). For pituitary tumor samples, the total RNAs were reverse transcribed to cDNA and used as templates for the RT-PCR. However, for parathyroid tumor RT-PCR templates, the total RNAs were subjected to one round of amplification prior to the cDNA synthesis. For insulinoma RT-PCR templates, we performed laser capture microdissection using PixCell IIe system on insulinoma tissue sections to obtain tumor and normal islets, isolated total RNA and performed cDNA synthesis. Our RT-PCR results showed decreased MEG3 expression in 13 out of 20 parathyroid samples (3 cancer, 6 hyperplasia, 4 adenoma) (p = 0.001-0.05). In pituitary tumors, PRL-secreting tumors from MEN1 patients showed less MEG3 compared to all 4 ACTH-secreting tumors. Analysis of sporadic insulinomas is in progress. Our results strongly indicate that MEG3 is silenced in sporadic or MEN1-associated endocrine tumor types supporting the tumor suppressor role of MEG3 in endocrine cells, and warrant further study to explore the possibility of restoring MEG3 expression as a potential therapeutic option or marker for the management of endocrine tumors. Citation Format: Sita D. Modali, Shruti S. Desai, Vaishali I. Parekh, Russel R. Lonser, Electron Kebebew, Michael Emmert-Buck, Sunita K. Agarwal. Reduced expression of the long non-coding RNA MEG3 in sporadic and MEN1-associated tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-249. doi:10.1158/1538-7445.AM2013-LB-249

Expression and Significance of E-Cadherin and β-Catenins in Pituitary Adenoma

This study used immunohistochemical methods for detecting the expression of E-cadherin and β-catenin in pituitary adenoma. Specimens were collected from 91 cases. EnVision was used for immunohistochemical staining. The results were graded depending on the staining intensity and range. Associations between E-cadherin and β-catenin expression and tumor subtype, invasiveness, and postoperative recurrence were investigated. There was a significant downregulation of E-cadherin and β-catenin in growth hormone (GH)-type tumors when compared with prolactin-type tumors (u(c) = 2.693 and 2.109, respectively; P < .05). E-cadherin and β-catenin were downregulated in invasive pituitary adenomas (u(c) = 3.563 and 4.166, respectively; P < .05) and in clinically recurring pituitary adenomas (u(c) = 2.871 and 3.866, respectively; P < .05). There was no difference in the percentage of invasive prolactin and GH secreting tumors (28.57% and 22.86%, respectively; P > .05). The expression of E-cadherin and β-catenin in pituitary adenoma was significantly downregulated and related to subtype, invasiveness, and postoperative recurrence.

Single-surgeon fully endoscopic endonasal transsphenoidal surgery: outcomes in three-hundred consecutive cases

The objective of this study was to evaluate outcomes of endoscopic transsphenoidal surgery using a single-surgeon technique as an alternative to the more commonly employed two-surgeon, three-hand method. Three hundred consecutive endoscopic transsphenoidal procedures performed over a 5 year period from 2006 to 2011 were reviewed. All procedures were performed via a binasal approach utilizing a single surgeon two handed technique with a pneumatic endoscope holder. Expanded enodnansal cases were excluded. Surgical technique, biochemical and surgical outcomes, and complications were analyzed. 276 patients underwent 300 consecutive surgeries with a mean follow-up period of 37 ± 22 months. Non-functioning pituitary adenoma (NFPA) was the most common pathology (n = 152), followed by growth hormone secreting tumors (n = 41) and Rathke's cleft cysts (n = 30). Initial gross total cyst drainage based on radiologic criteria was obtained in 28 cases of Rathke's cleft cyst, with 5 recurrences. For NFPA and other pathologies (n = 173) gross total resection was obtained in 137 cases, with a 92% concordance rate between observed and expected extent of resection. For functional adenoma, remission rates were 30/41 (73%) for GH-secreting, 12/12 (100%) for ACTH-secreting, and 8/17 (47%) for prolactin-secreting tumors. Post-operative complications included transient (11%) and permanent (1.4%) diabetes insipidus, hyponatremia (13%), and new anterior pituitary hormonal deficits (1.4%). CSF leak occurred in 42 cases (15%), and four patients required surgical repair. Two carotid artery injuries occurred, both early in the series. Epistaxis and other rhinological complications were noted in 10% of patients, most of which were minor and diminished as surgical experience increased. Fully endoscopic single surgeon transsphenoidal surgery utilizing a binasal approach and a pneumatic endoscope holder yields outcomes comparable to those reported with a two-surgeon method. Endoscopic outcomes appear to be better than those reported in microscope-based series, regardless of a one or two surgeon technique.

Medically treated prolactin-secreting pituitary adenomas: when should we operate?

Background. The incidence of medical failure for prolactin (PRL)-secreting pituitary tumours is not well known. Object. The purpose of this study is to report clinical, radiographic and laboratory findings of PRL-secreting tumours that predict failed medical management. Methods. An analysis of 92 consecutive patients was performed that met the inclusion criteria. Decision for surgery was made based on failure of dopamine agonists to either control clinical symptoms and normalise hormonal level or diminish mass effect on follow-up evaluation. Results. Of the 92 patients treated, 14 patients (15%) required trans-nasal, trans-sphenoidal pituitary surgery (TSS). One patient underwent surgery for repair of a skull defect and 13 patients (14%) required surgery after failed medical management. Higher initial PRL was statistically significant regarding the need for surgical intervention, but a persistently abnormal level after initiation of treatment was a more significant predictor (Fisher exact test, p = 0.005 vs. p < 0.001). Size was also a statistically significant factor (p = 0.014); macroadenomas had a relative risk of 9.27 (95% CI: 1.15–74.86) for needing surgery compared to microadenomas. In addition, macroadenomas with cavernous sinus (CS) extension and pre-operative visual field deficit demonstrated a strong tendency for surgical intervention. Conclusion. Medical management remains the most effective treatment option for prolactinomas. A partial hormonal response to medical management seems to be the most significant predictive factor but adenomas > 20 mm, visual field deficit and invasion of the CS may help predict the need for surgery. We suggest a minimum trial period (at least 8 weeks) of medical treatment prior to the consideration of surgery.

First demonstration of the effectiveness of peptide receptor radionuclide therapy (PRRT) with 111In-DTPA-octreotide in a giant PRL-secreting pituitary adenoma resistant to conventional treatment

In prolactin-secreting giant adenomas, cabergoline treatment is the first line approach. Surgery and/or radiotherapy are indicated when the tumour is resistant to medical treatment and continues growing, causing visual field impairment. Data concerning other therapeutic approach are scanty. Although PRL-secreting tumours may express somatostatin receptors type 2, 3 and 5, somatostatin analogs treatment is generally ineffective and peptide receptor radionuclide therapy (PRRT) has never been reported. A 58 year-old woman complaining of severe neurological symptoms caused by a giant prolactinoma, relapsing after surgery and not-responding to dopamine-agonists and octreotide LAR treatment, underwent four cycles of PRRT with 111-Indium-DTPA-octreotide with remarkable tumour shrinkage and a significant improvement in clinical conditions. No side effects were reported. This is the first report on the effectiveness and safety of PRRT with radio-labelled somatostatin analogs in a patient with aggressive giant prolactinoma resistant to conventional treatment.

Prolactin in men's health and disease

To review physiology of prolactin (PRL), cause and managment of hyperprolactinemia, and discuss evolving diverse roles of PRL in men's health. Hyperprolactinemia can be physiologically found after sexual activities, exercise, lactation, during pregnancy, and after stressful venipuncture. Elevated PRL can be caused by medications use, renal failure, hypothyroidism, and by prolactinoma - PRL secreting tumors. Symptomatic hyperprolactinemia and prolactinomas should be treated to lower PRL levels, decrease tumor size, and restore gonadal function. Three modes of treatment are typically utilized: pharmacological, radiosurgery with gamma radiation, and external beam radiation. Pharmacological treatment of prolactinomas is mainly based on dopamine agonists. The most frequently used dopamine agonists are bromocriptine and cabergoline. Cabergoline becoming the preferred drug in the treatment of prolactinomas because of higher response rate and less side-effects. Bromocriptine has been recently approved to improve glycemic control in diabetes mellitus. PRL plays a diverse role in men's reproduction and health. Detecting and treating elevated PRL may not only improve infertility and hypogonadism but also have a positive effect on the metabolic profile of patient and control of glycemic control and metabolic profile - an important advantage considering dramatic and worldwide increase in obesity and diabetes.

The Association of Pituitary Tumors and Headache

Pituitary tumors may give rise to headache via numerous mechanisms. The traditional explanation for headache is dural stretch and cavernous sinus invasion, although this is not borne out by clinical studies. Certain functional pituitary tumors are associated with headache, notably growth hormone and prolactin-secreting tumors. The observation that somatostatin analogues can have a dramatic analgesic effect in acromegaly suggests that biochemical properties of the tumor may be important. The genetic predisposition of the patient to primary headache also determines whether headache occurs with pituitary tumors. This article attempts to outline the clinical features, management strategies, and key academic questions regarding the subject of pituitary tumors and headache.

Treatment of pituitary adenomas using radiosurgery and radiotherapy: a single center experience and review of literature

Fractionated radiotherapy (FRT) and gamma knife stereotactic radiosurgery (GKSRS) are used as adjuvant therapies to surgical resection for functional and non-functional pituitary adenomas, although their optimum role in the treatment algorithm, as well as long-term safety and efficacy, still awaits further study. We report a single center experience with 33 patients with non-functional (16 patients), ACTH- (five patients), GH- (four patients), or prolactin-secreting (eight patients) tumors treated with FRT or SRS. The median tumor diameter was 1.9 cm, and the median follow-up was 36 months. For GKSRS, the median dosage was 16 Gy for non-functional adenomas and 23 Gy for hormone-secreting tumors. The median total dose for FRT was 50.4 Gy over 28 fractions (median). Two patients (6%) demonstrated radiographic evidence of tumor progression, three patients (9%) demonstrated radiation-induced visual field deficits on neuro-ophthalmic evaluation, and two patients (6%) suffered from radiation-induced hypopituitarism. Biochemical control, defined as normalized hormone values in the absence of medical therapy, was achieved in five out of eight prolactinoma patients and two out of five patients with Cushing's disease, but none of the four patients with acromegaly. These results are presented with a review of the relevant literature on the differential characteristics of FRT versus SRS in the treatment of functional and non-functional pituitary adenomas and validate postoperative irradiation as a potentially safe and effective means for tumor control.

A Double Pituitary Adenoma Presenting as a Prolactin-secreting Tumor with Partial Response to Medical Therapy. Case report

Double pituitary adenomas are difficult to recognize pre-operatively as only a single mass may be appreciated on imaging. We present herein a giant prolactin-secreting pituitary adenoma in a middle-aged man that had responded partially to dopamine agonist therapy. The excised specimen demonstrated a double adenoma. The prolactin-producing one displayed the expected morphological changes resulting from medical therapy, while the other, a gonadotroph adenoma, did not. The failure of tumor shrinkage can be attributed to the presence of a double adenoma, a previously unreported cause of failure of medical therapy in prolactinoma.

Endoscopic pituitary surgery: a systematic review and meta-analysis

Surgery on the pituitary gland is increasingly being performed through an endoscopic approach. However, there is little published data on its safety and relative advantages over traditional microscope-based approaches. Published reports are limited by small sample size and nonrandomized study design. A meta-analysis allows for a description of the impact of endoscopic surgery on short-term outcomes. The authors performed retrospective review of data from their institution as well as a systematic review of the literature. The pooled data were analyzed for descriptive statistics on short-term outcomes. Nine studies (821 patients) met inclusion criteria. Overall, the pooled rate of gross tumor removal was 78% (95% CI 67-89%). Hormone resolution was achieved in 81% (95% CI 71-91%) of adrenocorticotropic hormone secreting tumors, 84% (95% CI 76-92%) of growth hormone secreting tumors, and 82% (95% CI 70-94%) of prolactin secreting tumors. The pooled complication rates were 2% (95% CI 0-4%) for CSF leak and 1% (95% CI 0-2%) for permanent diabetes insipidus. There were 2 deaths reported in the literature that were both related to vascular injury, giving an overall mortality rate of 0.24%. The results of this meta-analysis support the safety and short-term efficacy of endoscopic pituitary surgery. Future studies with long-term follow-up are required to determine tumor control.

Kidney Damage in Rats Bearing an Adrenocorticotropin and Prolactin Secreting Tumor

The effect of chronic high plasma corticosteroids' concentration upon renal function was studied in rats bearing a transplantable pituitary mammotropic tumor which produces large quantities of ACTH and prolactin (MtTF4S). Kidney splanchnomegaly and degenerative changes of renal cortex, particularly in proximal tubules, as well as cytolysis and appearance of vacuoles were noticed in tumor bearing rats. (Na+ + K+)-ATPase activity in renal plasma membranes decreased 67% in rats with a tumor secreting ACTH and prolactin, and 64% in rats with a tumor secreting growth hormone and prolactin when compared with controls. After adrenalectomy of MtTF4S rats, kidney weight as well as plasma concentrations of urea, sodium, chloride and phosphate ions were normalized indicating the involvement of adrenal glands in the development of disturbances in renal function.

TUMOR TISSUE IDENTIFICATION IN THE PSEUDOCAPSULE OF PITUITARY ADENOMA

The microsurgical pseudocapsule can be found in the transition zone between an adenoma and the surrounding normal pituitary tissue. We investigated the precise histology of the pseudocapsule. Furthermore, we evaluated the remission rate, the changes in pituitary function, and the recurrence rate after intensive resection of the pseudocapsule. In 616 patients with pituitary adenomas (Hardy Types I-III) over a period of 14 years, we introduced intensive resection of the microsurgical pseudocapsule to achieve complete tumor removal. A combined pituitary function test and radiological study were performed on the patients before surgery, 1 year after surgery, and at subsequent 1.5-year intervals 2 to 13 years postoperatively. Microsurgical pseudocapsules were identified in 343 (55.7%) of 616 patients, and the distinct microsurgical pseudocapsules were observed in 180 (52.5%) of these patients. In the remaining 163 patients, the microsurgical pseudocapsules were incompletely developed. Tumor cluster infiltration was present in the pseudocapsule in 71 (43.6%) of these patients. Aggressive resection of the microsurgical pseudocapsule was more often required in larger tumors than in smaller ones. The presence of a pseudocapsule was slightly more frequent in prolactin-secreting tumors (70.9%) than in growth hormone-secreting (55.0%) and adrenocorticotropic hormone-secreting (40.0%) tumors. In the 243 patients of the total resection group who underwent combined pituitary function tests more than 2 times after surgery, the surgical remission rate was 99.1% in clinically nonfunctional tumors, 88% in growth hormone-secreting, 70.6% in prolactin-secreting, and 100% in adrenocorticotropic hormone-secreting tumors. The surgical remission rate was 86.2% in the presence of a pseudocapsule and 94.3% in the absence of a pseudocapsule. Preoperative hypopituitarism improved in 140 patients (57.6%), persisted in 47 patients (19.3%), and was aggravated in 33 patients (13.6%). There was no statistical difference in improvement or deterioration of pituitary function according to the existence or absence of the pseudocapsule. The tumor recurrence rate was 0.8% in the total resection group and was 42.1% in the subtotal resection group. We have shown that tumor tissue is frequently present within the pseudocapsule, suggesting that any tumor remnant in the pseudocapsule could be a source of recurrence and an obstacle to achieving complete remission. These results indicate that intensive resection of the pseudocapsule could result in a higher remission rate without deteriorating pituitary function.

Differential Expression of Somatostatin and Dopamine Receptor Subtype Genes in Adrenocorticotropin (ACTH)-secreting Pituitary Tumors and Silent Corticotroph Adenomas

Somatostatin analogs and dopamine agonists are clinically used for medical therapy of functioning pituitary tumors, such as growth hormone- and prolactin-secreting tumors, however, their effects on ACTH-secreting tumors are controversial. This study was aimed to determine whether somatostatin receptor (SSTR) subtype (1-5) and dopamine receptor type 2 (D2R) are differentially expressed in pituitary tumors causing Cushing's disease (CD), silent corticotroph adenoma (SCA), and non-functioning pituitary tumor (NFT). Tissue specimens were obtained from 35 pituitary tumors during transsphenoidal surgery. The steady-state mRNA levels of SSTR1-5 and D2R genes were determined by real-time reverse-transcription polymerase chain reaction. Both SSTR1 and 2 mRNA levels in SCA were greater than CD, while SSTR1 mRNA levels, but not SSTR2, in SCA were also greater than NFT. SSTR5 mRNA levels in CD were greater than SCA, but did not differ between NFT and SCA. SSTR4 mRNA expression was undetectable. D2R mRNA levels were markedly lower in CD and SCA than in NFT. The present study suggests that somatostatin analogs more selective for SSTR5 and for SSTR1 and/or 2may have the therapeutic potential for medical treatment of CD and SCA, respectively, whereas clinical application of dopamine agonists selective for D2R is very limited in either CD or SCA.

Index of Suspicion

Index of Suspicion