Growth hormone (GH) is essential for normal growth and development. It has been recognized that the synthesis and secretion of GH are regulated by hypothalamic growth hormone-releasing hormone (GHRH) and somatostatin (SS) . Complementary DNAs for these hormones and their receptors have recently been cloned, and the regulation of their expression has been studied extensively. Receptors for both GHRH and SS are associated with G proteins that regulate adenylate-cyclase activity, and thereby GH synthesis and secretion. In addition, a group of peptides (GH-releasing peptides [GHRPs]) with potent GH-stimulating activity has been synthesized. These peptides appear to stimulate GH secretion via protein kinase C (PKC). The recently identified GHRP receptors will stimulate the search for endogenous GHRPs that may be useful in the treatment of patients with some types of GH deficiency. In addition, the transcription factor pit-1 has been shown to be necessary for somatotroph development and GH synthesis. GH has a number of effects on carbohydrate, lipid, protein and electrolyte metabolism. These effects are mediated by GH receptors that are associated with the tyrosine kinase JAK 2 kinase. PKC is also utilized in GH-signalling. The extracellular domain of GH receptors (GH-binding protein [GHBP]) is detected in human serum. The growth-promoting action of GH is mediated mainly insulin-like growth factor I (IGF- I). IGF- I stimulates the growth and maturation of a number of cell types. IGF- I and its receptors are also involved in the growth of cancerous cells. It has been proposed that IGF-II is responsible for the hypoglycemia frequently associated with non-islet cell tumors. IGF- I and -II are complexed with IGF-binding proteins (IGFBPs) in the circulation. At least 6 species of IGFBP have been identified, but their physiological roles are as yet largely unknown.

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Recent methodological advances in immunohistochemistry, ultrastructural techniques, hormonal assays, resolution imaging and molecular biology techniques have provided new insights into the pathology, functions, and cytogenesis of pituitary adenomas. Pituitary adenomas have been classified historically on the basis of tinctorial affinities, followed by ultrastructure and immunohistochemistry. The current development of technologies necessitate a new classification of pituitary adenomas which integrates this enormous information as well as previous clinical information. We demonstrate here the molecular morphology of pituitary adenomas using a non-radioisotopic in situ hybridization technique. The expression of the pituitary-specific transcriptional factor (Pit-1), and nuclear receptors including estrogen receptor, thyroid hormone receptor and retinoid X receptor genes in adenomas are demonstrated. This new information provides deeper insights into understanding the pathophysiology and pathogenesis of adenomas. We propose a new clinico-cytofunctional classification of pituitary adenomas which is based on clinical manifestations and integrates the information concerning the biology, images, functions, and ultrastructure. This classification which corresponds to current advances will not only provide pertinent clinical information but will also facilitate better understanding of the biology and nature of these complex lesions.

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The goals of the transsphenoidal surgery include : 1) normalization of excessive pituitary hormone levels ; 2) decompression of the optic chiasm ; and 3) preservation of normal pituitary function. Surgical techniques for functioning adenomas basically do not differ from those for nonfunctioning adenomas. These techniques are described based on the authors' personal experiences of 500 transsphenoidal procedures.

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The author has experienced approximately 500 cases of transsphenoidal Surgery, of which one-thlrd were non-functioning pituitary adenomas. Based on this personal experience, the indication and surgical techniques of this procedure on the treatment of non-functioning adenomas is described. With a basic concept that the purpose of treatment of non-functioning adenomas is restoration of neurological and hormonal functions, surgery should be considered. Because of its benign nature, the author believes that attempts at radical removal of the tumor should not be performed at the cost of postoperative neurological and/or hormonal deficits. The most serious complication the author has experienced was postoperative swelling of the residual mass which caused compression of the hypothalamus and peritumoral bleeding. Swelling of the residual mass is believed to be caused by the obstruction of venous drainage in the adenoma. The author has experienced one death and another severely disabled case as a result of this phenomenon. Otherwise, when the surgery is properly indicated and properly performed, transsphenoidal surgery is a safe and effective choice of treatment in most cases with a non-functioning adenoma.

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Corticotropin-releasing factor (CRF) binds to the pituitary CRF receptor 1 (CRF-R1) and stimulates both synthesis and secretion of adrenocorticotropic hormone (ACTH) while vasopressin (VP) bincls to the V_<1b6gt; receptor and stimulates only ACTH secretion. Both CRF ard VP down-regulate CRF-R mRNA in the normal corticotroph, but up-regulates CRF-R mRNA in the corticotroph adenomd cells. 1-deamino-8-D-arginine-vasopressin (DDAVP), a V_2-R agonist, stimulates ACTH secretion from the corticotroph adenoma cells, but does not stimulate it from the normal pituitary cells. The DDAVP test is useful for screening of patients. with Cushing's disease. Some proopiomelanocortin (a precursor of ACTH) transcription activating factors are reported. These findlngs will open the way to gene therapy for Cushing's disease.

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Forty-three patients with the unilateral type of acoustic neurinoma treated by gamma knife radiosurgery were evaluated from the viewpoint of functional preservation of cranial nerves and complications. The follow-up period ranged from 22 to 55 months (mean 36 months). The tumors, which ranged in volume from 0.1 to 18.7 ml (mean 4.0 ml), were treated with marginal radiation doses of 9-15 Gy (mean 13.4 Gy) with multiple isocenters (mean 8.7). Functional hearing was preserved in 80% of patients, and actuarial hearing preservation rates were 83% at 1 year, 77% at 2 years, and 77% at 3 years after gamma knife radiosurgery. No factor was found to correlate with hearing deterioration using Cox's proportional hazards regression model. Transient facial and trigeminal neuropathies occurred in 2.3% and 4.7% of patients, respectively. Ten patients (23%) experienced transient dizziness 3 to 6 months after radiosurgery, but only preradiosurgery canal palsy was found to correlate with this using multiple regression analysis (p=0.02). Three patients developed communicating hydrocephalus, which may have been due to the high cerebrospinal fluid protein concentration (mean 149 mg/dl). Our results show that gamma knife radiosurgery should be considered as alternative therapy for patients with small- to medium-sized acoustic neurinomas, especially in those with functional hearing, due to the high cranial nerve function preservation rates achieved with this procedure.

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Complete resection of the wall of Rathke's cysts are frequently difficult to perform without surgical damage to vital structures around the cyst and postoperative leakage of cerebrospinal fluid. The cysts have reportedly been treated successfully with simple aspiration and partial excision of the cyst wall by the transsphenoidal approach. However, reaccumulation of the cyst content and recurrence of the symptoms have been documented following these operations. The simple open drainage method was performed by transsphenoidal surgery to avoid the reaccumulation of the cyst content against recurrent and hardly excised ones. We reported the efficacy and the problems of this new method. In this method, the sellar flore and the bottom of the cyst wall were opened as widely as possible following aspiration to the cyst contents and the cyst was left open into the sphenoid air cell without plasty of the sellar flore. No curretages or efforts to remove the cyst wall except for the inferior areas was performed (simple open drainage method). In 2 cases of symptomatic Rathke's cleft cyst treated with this procedure, visual field defects and diminished functions of the anterior pituitary lobe disappeared completely. However, diabetes insipidus followed and persisted for 1 to 3 months after the operations. This temporary diabetes insipidus was thought to be induced by the excess traction to the pituitary stalk due to the abrupt decompression of the cyst. The cyst was opened and drained into the sphenoid air cell and was demonstrated as a small intrasellar air collection by follow-up CT and MRI. Recurrent or hardly excised cysts with a thick and hard wall may be the best candidates for this method because the possibilities of postoperative empty sellar syndrome, cerebrospinal fluid leakage, and infection are thought to be minimal in these cysts.

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A case of nonfunctioning pituitary adenoma progressing to pituitary apoplexy after insulin-thyrotropinreleasing hormone (TRH)-luteinizing hormone-releasing hormone (LHRH) [ITL] test is reported. A 27-year-old male with pituitary macroadenoma was admitted to our hospital. An ITL test was performed in order to evaluate the preoperative hormonal condition. 0.1 U/kg of regular insulin, 500 μg of TRH and 100 μg of LHRH was injected intravenously. Three hours later, he began to complain of a headache. Fifteen and a half hours later, he noted visual impairment and bitemporal hemianopsia. An emergency CT scan showed an intratumoral hemorrhage with peritumoral bleeding. Transsphenoidal removal of the tumor was immediately performed. Pathological examination revealed a chromophobe adenoma with hemorrhage and necrosis. Here, we summarize the reported cases of pituitary apoplexy after pituitary stimulation test.

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We treated a 55-year-old female with multiple meningiomas who had undergone 3 surgeries since 1972. Although 1 meningioma (Simpson grade I) was completely extirpated in 1990, meningiomas recurred bilaterally. All 3 were completely resected (Simpson grade I). The estrogen and progesterone receptors (ER and PR) of the 3 meningiomas were measured by enzyme immunoassay. One small meningioma was ER positive, and all 3 were PR positive. The PR concentration was higher in the small- or medium-sized tumors than in the large one. The possibility of antiprogesterone treatment in tumors of this type is discussed.

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A case of rupture of an anterior communicating artery aneurysm associated with an accessory middle cerebral artery (AMCA) is reported. A 51-year-old woman presented with severe headache, nausea, vomiting, and disturbance of consciousness. Cardiovascular system examination revealed no abnormalities. Computed tomography (CT) scanning revealed diffuse subarachnoid hemorrhage, and right common carotid angiography showed a saccular aneurysm of the anterior communicating artery as well as an AMCA arising from the A1 segment. Frontotemporal craniotomy was performed, and the ruptured anterior communicating artery aneurysm was clipped successfully. On the 7th postoperative day, however, the patient suddenly lost consciousness. Left carotid angiography showed diffuse vasospasm affecting the C_2 portion of the internal carotid artery, middle cerebral artery, and anterior cerebral artery. The patient died on the 11th postoperative clay. The incidence of AMCA is reported to be 3% in angiographic series, and there have been only 23 previously reported cases of intracranial aneurysms associated with AMCA. The relevant literature and the treatment of cerebral aneurysms associated with AMCA are reviewed.

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