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Journal Article 2008; 29(1): 113-116 PubMed PMID: 18283262 Citation  Keywords:  Adenoma:metabolism, Adult, Aged, Female, Growth Hormone:metabolism, Hemangiopericytoma:metabolism, Humans, Male, Middle Aged, Pituitary Neoplasms:metabolism, Prolactin:metabolism, Receptors, Somatostatin:metabolism, Somatostatin:pharmacology, Tumor Cells,.   

OBJECTIVES: The aim of the study was to examine the effect of somatostatin (SST) on vascular endothelial growth factor (VEGF) secretion from clinically non-functioning pituitary tumors incubated in vitro.

MATERIAL AND METHODS: Eight pituitary tumors surgically removed were investigated. All of the tumors were diagnosed before surgery as non-functioning. Seven of them were diagnosed after surgery as pituitary adenomas and expressed either gonadotropins or their subunits as detected by immunohistochemistry. Two tumors additionally expressed prolactin and growth hormone. One tumor was immunonegative for pituitary hormones and was diagnosed as haemangiopericytoma. All tumors but one were investigated immunohistochemically to detect the somatostatin receptors and expressed at least 3 of 5 subtypes of somatostatin receptors. The cells isolated from the examined tumors were exposed in vitro to native SST-14. The concentration of VEGF in the culture media was performed by means of ELISA method.

RESULTS: It was found that the exposure on SST-14 resulted in the divergent changes (increase in 4 cases and decrease in 3 cases) in VEGF concentrations in the medium. It seems that the inhibition of VEGF secretion is related to the expression of somatostatin receptor subtypes sst1 and sst2.

CONCLUSIONS: The response of VEGF secretion from pituitary tumoral cells to SST seems to depend on the spectrum of expressed somatostatin receptor subtypes. However, this presumption needs further studies on the larger material....

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Journal Article 2007; 28(6): 841-845 PubMed PMID: 18063932 Citation  Keywords:  Adult, Dopamine Agonists:adverse effects, Female, Follow-Up Studies, Humans, Intracranial Hemorrhages:etiology, Magnetic Resonance Imaging, Male, Pituitary Neoplasms:blood, Prolactin:blood, Prolactinoma:blood, Radiography, Receptors, Dopamine D2:agonists,.   

OBJECTIVES: Retrospective follow-up study on patients suffering from macroprolactinomas which were treated with agonists of D2 receptors; the MRI results were correlated with the clinical symptomatology and with the level of prolactin in the blood.

METHODS: From 1996 to 2006 we followed 38 patients diagnosed with macroprolactinoma. All patients underwent MRI in same protocol two times. The indication for MRI was based on the clinical symptomatology (signs of hormonal dysfunction, visual fields impairment) or increased blood level of prolactin.

RESULTS: The first predominant clinical signs in males were local manifestations of expansive process and in women hormonal dysfunction. Intratumorous haemorrhage in patients undergoing the treatment with the agonists of D2 receptors is common, it was encountered in 25 cases, but only in two cases it was followed by a more serious clinical symptomatology, which had to be referred to the department of the neurosurgery. Even when there were pronounced regressions or near complete disappearance of the tumour and normalisation of the blood level of prolactin, withdrawal of the treatment with agonists of D2 receptors caused increase in size of the adenoma and increase of level of prolactinaemia.

CONCLUSION: Only two patients presented with serious clinical symptomatology associated with intratumoral hemorrhage. The hemorrhages are more common during the first weeks of therapy, but can happen at any time thought out the treatment with D2 receptor agonists. Our hypothesis: the prolactinomas with higher level of prolactin have greater tendency for larger hemorrhages....

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Case Reports 2007; 28(5): 560-564 PubMed PMID: 17984954 Citation  Keywords:  Adenoma:pathology, Adult, Antineoplastic Agents, Hormonal:therapeutic use, Choristoma:pathology, Growth Hormone-Secreting Pituitary Adenoma:pathology, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Peptides, Cyclic:therapeutic .   

: MR spectroscopy (MRS) of hormonally active pituitary adenomas has not been published in literature. We report MR imaging and spectroscopy findings in a 41-year-old man with extrapituitary growth hormone-secreting adenoma. Application of the single voxel proton MRS, SE 135 technique, with voxel size 11x11x11 mm, revealed the elevated choline peak (resonance at 3.2 ppm) in the paramedial aspect of the tumor, while no metabolic activity in the mentioned region was noted using the same method 11 months after Lanreotide treatment. Elevation of choline peak in functional pituitary adenomas could represent an active marker of cellular proliferation, compatible with increased hormonal activity....

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Case Reports 2007; 28(5): 549-553 PubMed PMID: 17984930 Citation  Keywords:  ACTH-Secreting Pituitary Adenoma:blood, Adenoma:blood, Adrenocorticotropic Hormone:blood, Aged, Antineoplastic Agents, Hormonal:therapeutic use, Empty Sella Syndrome:blood, Female, Humans, Octreotide:therapeutic use, Pituitary Neoplasms:blood, Treatment F.   

BACKGROUND: Our patient was a 65-year-old woman previously diagnosed with Addison's disease. She presented an empty sella turcica and, at the age of 47, was discovered to have autonomous hypersecretion of adrenocorticotropic hormone (ACTH), suggesting a corticotropic adenoma secondary to Addison's disease, with a lack of response to high levels of dexamethasone. She maintained high ACTH levels despite corticosteroid treatment.

METHODS: The patient underwent a CRH stimulation test using an intravenous bolus (100 microg) with samples every 30 minutes for 3 hours and, the day after, an octreotide infusion (0.1 mg/200 cc saline) for 2 hours with measurements every 30 minutes for 3 hours. The following month she received subcutaneous octreotide 0.1 mg tid., and samples were taken every week.

RESULTS: Thirty minutes after the corticotropic-releasing-hormone (CRH) stimulation test, baseline ACTH levels (1 063 pg/ml) increased to 1530, the other values lying between 1 020-862. After octreotide infusion, baseline ACTH (1 212 pg/ml) was 946-643-1 630-4 600-1 730 at 30-60-90-120-180 minutes. The following month, with octreotide treatment, serum ACTH levels were 454-768-1233-429 pg/ml each week.

DISCUSSION: Octreotide acts mainly on somatostatin type 2 receptors (SSTR2) and has no effect in Cushing's syndrome, although a suppressor effect in some ACTH ectopic hypersecretions and in Nelson's syndrome has been demonstrated. It has been observed that SSTR5 appear more frequently than SSTR2 in corticotropic adenomas and corticosteroids downregulate octreotide sensitivity.

CONCLUSIONS: Octreotide did not suppress secretion of ACTH in suspected corticotropic adenoma. Newer somatostatin analogues, acting mainly on SSTR5, may be able to control ACTH hypersecretion in cases such as this....

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Journal Article 2007; 28(4): 382-385 PubMed PMID: 17693986 Citation  Keywords:  Animals, Biological Assay:methods, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme Stability:physiology, Growth Hormone:metabolism, Growth Hormone-Releasing Hormone:analogs & derivatives, Male, Pituitary Gland:cytology, Rats, Rats, Inbred WKY,.   

OBJECTIVE: It has been found that hGH-RH analogues with increased resistance to enzymatic degradation have a much higher potency than the native hGH-RH (1-29)-NH2 and have an ability to partially reverse growth hormone deficiencies.

THE AIM: The aim of these studies was to elaborate a method which can be used for preliminary evaluation of new GH-RH analogues both from the point of view of their potency to release GH and enzymatic stability.

METHOD: Two highly active GH-RH analogues with increased resistance to trypsin-like enzymes, and hGH-RH(1-29)-NH2 used as a standard, in doses 1 nM, 10 nM, and 100 nM were added to pituitary rat cell culture, and medium was collected after 30, 60, 120 and 240 min. GH concentration was measured by RIA kit.

RESULTS: It was observed that the potency of these two GH-RH analogues was several times higher than that of native compound. Moreover, the stimulation was much longer. This suggests that high activity of these analogues in vivo could be the result of increased enzymatic stability.

CONCLUSION: This method can be used for selecting more potent and more stable releasing peptides before in vivo evaluation....

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Journal Article 2007; 28(4): 438-444 PubMed PMID: 17693972 Citation  Keywords:  ACTH-Secreting Pituitary Adenoma:pathology, Adenoma:pathology, Adolescent, Adult, Aged, Child, Endoscopy:adverse effects, Female, Growth Hormone-Secreting Pituitary Adenoma:pathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Minimally Invasi.   

AIM OF THE STUDY: The paper presents endoscopic surgical technique used in the treatment of hormonally active pituitary adenomas and assessment of the method in terms of its effectiveness and safety.

MATERIAL AND METHODS: In 217 cases the surgery was performed due to pituitary adenomas applying the technique developed by Jho and Carrau, with our own modifications. 70 patients were treated for hormonally active adenomas. The group consisted of 36 somatotrophic adenomas, 21 prolactinomas and 13 corticotrophic adenomas. There were 51 females and 19 males with mean age of 42.6 years (range 11-77 years). The follow-up period was between 7 and 56 months (mean - 34 months). The effectiveness and occurrence of complications were confirmed on the basis of neurosurgical, laryngological, endocrinological, ophthalmological examinations and neuroimaging.

RESULTS: Biochemical and neurosurgical criteria for complete resection were obtained in 21 (58.3%) of 36 patients with all somatotrophic adenomas. In the group of prolactinomas complete resection was achieved in 17 (80.9%) of 21 patients. Of the 13 patients with Cushing's disease 11 (84.6%) were cured. In the studied group there were no deaths. In the postoperative course only 2 (2.8%) patients suffered liquorrhoeas and new anterior lobe pituitary insufficiency was noted in 8 (11.4%) cases. Meningitis was noted in 1 (1.4%) case and another 1 (1.4%) patient had epistaxis which required repeated endoscopic surgery.

CONCLUSIONS: Endoscopic technique is an effective method of treatment of hormonally active pituitary adenomas. It is characterised as being minimal invasive and has a low severe complication rate....

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Comparative Study 2007; 28(2): 166-169 PubMed PMID: 17435668 Citation  Keywords:  Adiponectin:blood, Animals, Inflammation:chemically induced, Injections, Intraperitoneal, Lipopolysaccharides, Male, Pituitary Adenylate Cyclase-Activating Polypeptide:administration & dosage, Rats, Rats, Inbred WKY,.   

BACKGROUND: Pituitary adenylate cyclase activating peptide (PACAP 38) is a neuropeptide with anti-inflammatory activity. Vasoactive intestinal peptide (VIP)/PACAP receptors are found in immune cells, endocrine glands and also in adipose tissue. Adiponectin is an adipocyte-derived protein hormone which possesses anti-inflammatory, antidiabetic and antiatherogenic properties. The aim of this study was to examine the influence of PACAP 38 on adiponectin release in basal conditions and during lipopolysaccharide (LPS)-induced acute inflammation.

METHODS: Male Wistar-Kyoto rats were divided into four groups which received intraperitoneal injections of 0.9% NaCl, LPS, PACAP 38 or LPS+PACAP 38, respectively. Serum adiponectin concentrations were measured using an ELISA test.

RESULTS: LPS administration did not change adiponectin concentration; however, PACAP 38 administered alone decreased serum adiponectin concentration after 2 h (p<0.05) and 4 h (p<0.01). In the group that received LPS+PACAP38, compared with LPS alone, no difference in adiponectin concentration was observed.

CONCLUSIONS: We conclude that PACAP 38 may directly modulate adiponectin secretion by adipocytes in basal conditions....

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Case Reports 2006; 27(6): 733-736 PubMed PMID: 17187002 Citation  Keywords:  Adrenocorticotropic Hormone:blood, Female, Follicle Stimulating Hormone:secretion, Gonadotrophs:pathology, Humans, Hydrocortisone:blood, Magnetic Resonance Imaging, Middle Aged, Neoplasms, Multiple Primary:pathology, Pituitary ACTH Hypersecretion:blood, P.   

OBJECTIVE AND IMPORTANCE: We encountered a Cushing's disease patient whose surgically removed pituitary macroadenoma was not an ACTH-producing, but rather a gonadotroph adenoma. Cure was obtained only after a tiny microadenoma, overlooked on preoperative studies, was removed by a 2nd operation from a compressed thin normal anterior pituitary gland.

CLINICAL PRESENTATION: This 45-year-old woman with Cushing syndrome presented with diabetes mellitus and steroid psychosis. Endocrinological examinations suggested Cushing's disease and MRI disclosed an invasive macroadenoma (22 mm in diameter) with suprasellar extension.

INTERVENTION: Despite total removal of the invasive macroadenoma by transsphenoidal surgery, her elevated serum cortisol- and ACTH levels failed to decrease. Histologic study of the surgical specimen disclosed that the tumor was a silent FSH-producing, rather than an ACTH-producing adenoma. Detailed re-evaluation of pre- and postoperative MRI suggested the presence of a 3-mm microadenoma on the left side of a thin compressed normal gland. Venous sampling of the cavernous sinus confirmed this suspicion. In a 2nd operation an ACTH-producing microadenoma was removed from inside the thin remaining compressed normal pituitary gland and endocrinological cure of Cushing's disease was achieved.

CONCLUSION: Although double adenomas, being a non-ACTH producing macroadenoma associated with an ACTH producing tiny microadenoma, are extremely rare in patients with Cushing's disease, detailed preoperative MRI evaluation is necessary to avoid missing tiny adenomas hidden in a compressed normal pituitary gland which is the cause of Cushing's disease, especially when a macroadenoma is found in patient with Cushing's disease....

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