Intrapituitary distribution and effects of annexin 5 on prolactin release

Annexin 5 is expressed by rat anterior pituitary cells and a depolarizing stimulus results in increased extracellular display and, depending on local calcium concentrations, potential release into the extracellular environment. In order to further investigate the role of annexin 5 in anterior pituitary function, we have examined the intracellular distribution by immunocytochemistry and the effects of annexin 5 on the release of a major secretory product, prolactin. Prolactin was chosen because we could easily monitor effects on basal release and effects on the immediate and sustained phases of thyroid stimulating hormone releasing hormone (TRH)-stimulated release. Immunocytochemical localization of annexin 5 showed staining of the majority of anterior pituitary cells. Labeling was predominantly on the nuclear envelope and plasma membrane. For the chosen secretory product, prolactin, annexin 5 was found in most, but not all prolactin positive cells. When recombinant annexin 5 (50 ng/mL) was added to a 3 h static culture incubation of rat anterior pituitary cells, prolactin release was inhibited by about 30% (p<0.05). A lower dose had a reduced effect and higher doses had no further inhibitory effect, indicating that the effect was specific to annexin 5 and not a nonspecific toxic effect of some contaminant in the preparation. This interpretation was further strengthened in a time-course experiment demonstrating that when TRH and annexin 5 were added together, there was no effect of annexin 5 on the amount of prolactin released. After a 3 h preincubation in annexin 5, however, prolactin release, in response to TRH, was suppressed by about 30% in both the acute and sustained phases. These data suggest that annexin 5 may be a local regulator of release in the anterior pituitary, but a slow onset effect on both phases of TRH-stimulated release suggests that this is not an effect at the plasma membrane such as local extracellular calcium depletion by plasma membrane-bound annexin 5.     

Plasmacytoma: An Unusual Cause of a Pituitary Mass Lesion. A Case Report and a Review of the Literature

A sixty six year old female presented with headache and decreased hearing. Clinical examination confirmed the presence of impaired hearing on the left side. Visual fields were full to confrontation and corrected visual acuity was normal. CT scan of brain revealed a pituitary mass. Preoperative anterior pituitary function was normal. Transsphenoidal decompression was performed, and histology was that of a plasmacytoma. Post operative pituitary function was normal. The patient had no symptoms or signs of multiple myeloma and subsequent investigations revealed no evidence of the disease. One year after diagnosis a course of radiotherapy was administered for local tumour recurrence. During seven years of follow-up, no evidence of multiple myeloma has emerged. Only thirteen similar cases have been described. Four of these had evidence of multiple myeloma at presentation and six progressed to it during follow-up. In twelve patients cranial nerve deficits were recorded. In any cases where it was documented, preoperative anterior pituitary function was normal. In a number of cases histology was reported initially as being that of a non-functioning adenoma, the true diagnosis being discovered, either by electron microscopy findings or after the development of multiple myeloma. Plasma cell tumours of the pituitary area are rare and can present with symptoms and signs indistinguishable from non-functioning adenoma. Atypical symptoms such as cranial nerve involvement or unexpected preservation of anterior pituitary function should arouse suspicion.     

A rare case and a rapid tumor response to therapy: dramatic reduction in tumor size during octreotide treatment in a patient with TSH-secreting pituitary macroadenoma

Thyrotropin (TSH)-secreting pituitary adenomas are the less frequent form of presentation of pituitary tumors. The presence of somatostatin receptors on TSH-secreting adenomas allows treatment of central hyperthyroidism with somatostating analogs. We report a 21-yr-old woman with TSH-secreting pituitary macroadenoma, who was diagnosed based on the symptoms of hyperthyroidism, the lack of inhibition of serum TSH despite an increased serum free thyroxine (FT₄), a low response of serum TSH to thyrotropin-releasing hormone, and a pituitary tumor as revealed by magnetic resonance imaging. The treatment with the somatostatin analog octreotid resulted in inhibition of serum TSH and FT₄ to euthyroid levels with concomitant clinical improvements such as the disappearance of sweating, tachycardia, and finger tremors within 7 d. The tumor size diminished dramatically within 6 wk during treatment of one monthly im injection of 20 mg octreotide-LAR. These effects were continued over 2 yr after the start of octreotide-LAR therapy. Therefore, octreotide-LAR appears to be a useful therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary tumors.     

Lymphoma Metastasizing to the Pituitary: An Unusual Presentation of a Treatable Disease

Lymphoma involving the pituitary gland is particularly rare. We present two cases of patients with pituitary lymphoma, both of whom were symptomatic from pituitary dysfunction. The first patient demonstrated pituitary involvement on imaging, with mild biochemical diabetes insipidus but clear hypoadrenalism. Both adrenals were grossly enlarged on CT scanning and biopsy of one of the adrenal masses confirmed the diagnosis of diffuse large B cell lymphoma. The second patient presented with clinical diabetes insipidus but with no obvious abnormalities on pituitary imaging. CT scanning of abdomen and pelvis, however, revealed widespread lymphadenopathy. Lymph node biopsy revealed a T cell-rich B cell lymphoma. Review of the English-language literature of all published cases of pituitary lymphoma in the presence of generalised disease in immunocompetent patients revealed 13 cases. Most patients had large B cell non-Hodgkin's lymphoma. Involvement of the anterior lobe of the pituitary was more frequently seen than in patients developing pituitary metastases from solid tumour primaries. Patients with advanced lymphoma including the pituitary also appear to have a better prognosis than patients presenting with pituitary metastases. This is an important diagnosis to make as rapidly as possible to allow the early institution of effective therapy.     

Estrogens modulate the inhibitory effect of tumor necrosis factor-alpha on anterior pituitary cell proliferation and prolactin release

Considering that tumor necrosis factor-alpha (TNF-alpha) is involved in normal tissue homeostasis and that its receptors are expressed in the anterior pituitary, we examined the effect of this cytokine on pituitary cell growth. Because anterior pituitary function depends on hormonal environment, we also investigated the influence of gonadal steroids in the effects of TNF-alpha on cell proliferation and the release of PRL from anterior pituitary cells. In addition, the release of TNF-alpha and its action on the release of PRL from anterior pituitary cells of rats at different stages of the estrous cycle was evaluated. In minimum essential medium D-valine, a medium that restricts fibroblastic proliferation, TNF-alpha (10 and 50 ng/mL) reduced 3H-Thymidine incorporation, DNA content, and active cell number. TNF-alpha failed to affect proliferation of cells from ovariectomized (OVX) rats. However, it significantly inhibited growth of cells from OVX rats cultured with 17beta-estradiol (E2) (10(-9) M) and from chronically estrogenized rats. TNF-alpha decreased the release of PRL from cells of intact rats, especially in proestrous, OVX rats cultured with E2 and chronically estrogenized rats. The release of anterior pituitary TNF-alpha was higher in proestrous rats. These results indicate that TNF-alpha plays an inhibitory role in anterior pituitary cell growth and the release of PRL in an estrogen-dependent manner.     

Double Pituitary Adenomas: Six Surgical Cases

While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3–6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3–6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.     

Pituitary Apoplexy in a Patient with Acute Myeloid Leukemia and Thrombocytopenia

We describe a 72-year-old woman with a history of acute myeloid leukemia who developed pituitary apoplexy associated with thrombocytopenia secondary to chemotherapy. She presented with new onset severe headache, nausea, vomiting and blurred vision. Initial physical examination was unremarkable. CT scan of the head was initially negative. Upon admission for further work up, She developed a high-grade fever, hypotension and obtundation. Subsequent physical examination revealed bitemporal visual fields defects and decreased visual acuity. Repeat imaging of head revealed a hemorrhagic pituitary mass compressing the optic chiasm. Laboratory results were compatible with the diagnosis of pan-hypopituitary syndrome. She received high dose steroids and was transferred for transnasal sphenoidotomy decompression surgery. The visual defects improved postoperatively. A literature review of Pituitary apoplexy is presented. Pituitary apoplexy secondary to thrombocytopenia has never been reported.     

小骨瓣纵裂入路显微外科手术切除巨大侵袭性垂体瘤14例报道

目的探索巨大侵袭性垂体腺瘤根治性切除的手术入路、方法及效果.方法选择14例巨大侵袭性垂体腺瘤采用小骨瓣经纵裂显微外科手术,肿瘤最大径4.2 cm～5.7 cm.结果肿瘤全切11例,大部切除3例.全部病例术后无脑脊液漏,无严重并发症,无死亡.结论小骨瓣纵裂入路显微外科手术切除巨大侵袭性垂体腺瘤是对脑组织损伤小、并发症少、全切率高的手术方法.     

Cysteamine-a somatostatin-inhibiting agent-induced growth hormone secretion and growth acceleration in juvenile grass carp (Ctenopharyngodon idellus)

Effects of cysteamine hydrochloride (CSH)-a somatostatin-inhibiting agent on growth hormone (GH) secretion from pituitary fragments (PF) or hypothalamus plus pituitary fragments (HPF) under static incubation conditions, serum GH, 3,5,3(')-triiodothyronine (T(3)) and thyroxine (T(4)) levels, and growth in juvenile grass carp (Ctenopharyngodon idellus) were investigated. CSH (0.1, 1, and 10 mM) had no influences on GH release from PF after 1 and 6h incubation, but was effective in stimulating GH release from HPF in a dose-dependent manner after 1 and 6h incubation. Moreover, prolonged treatment of HPF with CSH decreased the magnitude of enhancement of GH levels in culture medium. CSH and neuropeptides [e.g., human GH-releasing hormone (hGHRH, 100 nM), luteinizing hormone-releasing hormone analog (LHRH-A, [D-Trp(6),Pro(9)]LHRH, 100 nM)], or salmon gonadotropin-releasing hormone analogue (sGnRH-A, [D-Ala(6),Pro(9)]LHRH, 100 nM), alone and in combination during static incubation stimulated GH release from HPF after 1h incubation; in addition, there was an additive, not a synergistic effect of CSH and neuropeptides on stimulation of GH release. Administration of CSH (2.5mg/g diet) in combination with LHRH-A (5 microg/g diet) in diet twice daily for 8 weeks resulted in higher serum GH, T(3), and T(4) levels, ratio of RNA/DNA in muscle, food conversion efficiency, and growth rate than CSH or LHRH-A alone. At trial termination, significant decreases in condition factors and body lipid levels were observed in fish fed with CSH and/or LHRH-A. No significant differences were recorded for viscero-somatic index, hepato-somatic index, and percent body moisture and protein in muscle. These findings, taken as a whole, strongly suggest that the action of CSH stimulating GH release in vitro appears to be mediated through hypothalamic pathways and dietary delivery of CSH directly or indirectly stimulates endogenous GH, T(3), and T(4) secretion, and subsequently leads to a increase in growth rate in grass carp.