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Rhinological findings following transantrosphenoidal surgery of the pituitary gland.

Fifty patients with pituitary gland tumours on whom we operated via the transantrosphenoidal route, were rhinologically followed up with a view to revealing any conceivable functional impairments incurred by this method. Our investigations included rhinoscopy, endoscopy of the nasal and paranasal cavities and of the epipharynx, X-ray controls, and probes of the nn. olfactorius and trigeminus. Apart from the technical advantages of transantrosphenoidal pituitary gland surgery, the results also confirmed its benefit to functional performance.

Adenoma↗

Embryonic development of the pituitary gland in the chick.

Pituitary glands of chicken, from stages 20 (70 approximately 72 h of incubation) to 46 (20 days) of Hamburger and Hamilton (1951), were studied by immunocytochemical and histological stainings and India ink injection into blood vessels. Using the distribution pattern of 6 types of immunoreactive adenohypophyseal cells and the location of pituitary stalk as guideposts, we found how specific areas in the epithelium of Rathke's pouch differentiate into specific regions of the adenohypophysis at 20 days. In the sagittal plane, the walls of Rathke's pouch were tentatively divided into the upper part (A(1) + A(2)) and lower part (A(3)) of the anterior wall, and the posterior wall (P(1) + P(2) + P(3)). The cephalic lobe was mainly assembled by the proliferation of parenchymal cells in the areas A(2) + A(3) + P(2) of Rathke's pouch epithelia at 3 days of incubation. The caudal lobe was derived from A(1) + P(1) + P(3). The pars tuberalis was derived from A(1) + A(2). Thus, the avian adenohypophysis is established at 13 days, though the blood supply to the pars distalis is established at 20 days. Therefore, the cephalic lobe and caudal lobe of the pars distalis and the pars tuberalis of the chicken adenohypophysis are derived from specific areas of the cell cords of Rathke's pouch at 3 days of incubation.

Animals↗

MRI of pituitary adenomas: the position of the normal pituitary gland.

The position of the normal pituitary gland, assessed using gadolinium - enhanced MRI was compared with the position found at surgery for pituitary adenoma in 25 patients. The tumours were five microadenomas and 20 macroadenomas. Using T1-weighted imaging, the anterior lobe could be differentiated on the sagittal image in five patients (20%) and on the coronal image in four (16%). The high intensity of the posterior lobe could be differentiated using T1-weighted sagittal imaging in 13 patients (52%). The normal pituitary gland, which enhanced more strongly than tumour, could be differentiated using Gd-DTPA-enhanced MRI on the sagittal images in 22 cases (88%) and on the coronal image in 17 (68%). In seven patients, the normal pituitary gland surrounded the tumour; it was displaced superiorly in 14 cases and superioposterorly in two but in no case was it displaced anteriorly or downwards.

Adenoma↗

Is insulin growth factor-1 (IGF-1) playing a role for aneurysm formation in patients with pituitary gland tumor?

The combination of pituitary gland tumor and aneurysmal disease has previously been described. Most of these aneurysms have affected intracranial arteries. The purpose is to present 2 patients with thoracoabdominal aortic aneurysm and pituitary gland tumor and further to discuss the mechanism behind this combination of diseases. A 59-year-old male patient was admitted with abdominal pain and a 120 mm thoracoabdominal aortic aneurysm type III. He was operated with resection and graft replacement. During the operation, it was noted that his intra-abdominal arteries were extremely enlarged. The diagnosis acromegaly was confirmed in the late 50's and he had received irradiation therapy and underwent partial trans-sphenoidal hypophysectomy. His growth hormone values eventually declined while he had elevated insulin growth factor-1 (IGF-1) levels. The patient died from stroke 6 years after operation. Patient n. 2 is a 73-year-old female with a type II thoracoabdominal aortic aneurysm. She was operated for a pituitary adenoma in 1988. There were no clinical or biochemical signs of acromegaly. However, she had elevated serum values of IGF-1. The maximum diameter of the aneurysm was 60 mm. Because of comorbidity the patient has been followed at the outpatient clinic. The mechanism behind the combination of pituitary gland tumor and aneurysm is obscure. One of our patients had classical acromegaly. Growth hormone decreased over the years, while his IGF-1 values were normal or elevated. The other patient had increased levels of IGF-1 without typical acromegaly. This might indicate that IGF-1 could play a role in the development of aneurysm in patients with pituitary tumor. This combination of diagnoses should be kept in mind when dealing with patients having aneurysmal disease.

Adenoma↗

Pharyngosellar pituitary: a rare developmental anomaly of the pituitary gland.

A rare malformation of the pituitary gland, termed pharyngosellar pituitary, is reported. The anterior pituitary gland was continuous from the pharyngeal roof to the sella turcica. This was found in a male fetus of gestational week 17 with an encephalocele and amnion adhesion malformation syndrome. The distribution of hormone-producing cells in the malformed pituitary tissue was irregular: thyrotropic hormone-, follicle-stimulating hormone- and luteinizing hormone-producing cells were nearly absent in the sellar and middle sections of the pituitary but were found in small numbers mainly in the pharyngeal section of the pituitary. The teratogenic determination period was estimated at between weeks 4 and 8 of gestation.

Abnormalities, Multiple↗

[Pituitary gland tumors].

Pituitary adenomas must be clearly differentiated from other tumors of the sellar region (especially meningiomas, granular cell tumors, chordomas and germinomas), which may look very similar. The sub-classification of adenomas depends on the methods used, in particular the immunostaining for pituitary hormones. This sub-classification is not necessary in every case, but must be performed if unusual findings are observed during surgery or if surgery is unsuccessful and radiation or drug-therapy is planned. Special structures and non-immunohistochemical stainings are very helpful for typing adenomas. We differentiated monohormonal densely or sparsely granulated GH-cell adenomas, monohormonal sparsely or very rarely densely granulated prolactin cell adenomas, monohormonal densely or sparsely ACTH-cell adenomas, monohormonal TSH-cell adenomas and FSH/LH cell adenomas from bihormonal adenomas of mammosomatotroph or GH/prolactin cell type or of the acidophil stem cell adenoma type. The number of plurihormonal adenomas decreased with the use of improved monoclonal antibodies. Clinically inactive adenomas are classified as null cell adenomas, oncocytic adenomas or FSH/LH-cell adenomas. These appear as subtypes of one entity deriving from the gonadotroph cell type. Craniopharyngiomas are classified into adamantinous and papillary types, which are not only structurally but also clinically different. If adamantinous craniopharyngiomas show very strongly regressive changes, immunostaining for keratin may be necessary to identify the squamous epithelia for the demonstration of craniopharyngioma.

Adenoma↗

CT appearance of the adolescent and preadolescent pituitary gland.

Coronal computed tomographic scans of the pituitary gland in 27 normal children, adolescents, and young adults (ages, 8-21 years) and in a comparison group of adults (ages, 24-91 years) were evaluated retrospectively to test the applicability of published criteria for size and configuration of normal adult pituitary glands to younger patients. Statistically significant differences were found between the two groups, indicating that the pituitary gland in adolescents, particularly girls, is larger than in younger or older patients. The authors suggest that pubertal pituitary hyperplasia accounts for these findings. They conclude that standards for normal pituitary glands are probably inappropriate for adolescents.

Adenoma↗

Dopaminergic inhibition of prolactin release from pituitary glands of the domestic fowl incubated in vitro.

Anterior pituitary glands from broiler fowl were incubated by themselves, with hypothalamic tissue or with thyrotrophin releasing hormone (TRH) in medium containing dopamine and its antagonist pimozide. The presence of hypothalamic tissue or TRH resulted in a stimulation of release of prolactin. Neither dopamine nor pimozide affected prolactin release directly from the pituitary gland. Dopamine inhibited the release of prolactin stimulated by hypothalamic tissue or TRH, in a concentration-dependent fashion. Pimozide diminished the response to dopamine. After pituitary glands were preincubated for 20 h in medium containing oestradiol-17 beta, the basal release of prolactin was enhanced as was the response to TRH. Both basal and TRH-stimulated release of prolactin from the oestrogen-primed pituitary glands was inhibited by dopamine, an effect blocked by pimozide. Hypothalami from broiler fowl were incubated for up to 8 h in medium containing dopaminergic drugs and pituitary glands were incubated in this medium, alone or with pimozide. As indicated by the prolactin released by the pituitary glands, the hypothalami appeared to secrete prolactin-releasing activity in a time-related fashion. Dopaminergic activity was also present in the hypothalami, since pimozide enhanced the prolactin-releasing activity of the medium. Dopamine apparently inhibited and pimozide stimulated the secretion of releasing activity from the hypothalamus. These results suggest that dopamine inhibits release of prolactin directly from the pituitary gland only when prolactin secretion is high. The hypothalamus secretes at least two factors regulating prolactin secretion, a prolactin-releasing factor and a dopaminergic prolactin-inhibiting factor. Dopamine may also play an inhibitory role in the regulation of secretion of the prolactin-releasing factor.

Animals↗

[MRI of normal pituitary glands and their surrounding structures].

Normal MRI appearances of the pituitary glands and their surrounding structures were evaluated in 332 patients without sellar and parasellar diseases. The height of the pituitary gland was maximum at 10-19 years of age reflecting hormonal activity. The width of the pituitary gland decreased, while that of the cavernous sinus increased with aging. This is probably due to atherosclerotic change of the internal carotid artery. Females younger than 30 years of age tended to show a convex upper surface of the pituitary gland and the displacement of the pituitary stalk was common after 50 years of age. Almost all of the anterior lobe of the pituitary gland showed isointensity relative to the pons or cerebral cortex and the majority (85.1%) of the posterior lobe showed hyperintensity. However, the anterior lobe in 2 newborns showed hyperintensity similar to the normal posterior lobe in adults. The posterior lobe was located off the midline in 19.1% of the subjects. One case of pars intermedia cyst was discovered among 14 subjects who were administered Gd-DTPA. The dural membrane between the pituitary gland and cavernous sinus was recognizable only in 8.6% on the right side and 7.5% on the left side. Primary empty sella was identified in 4.5%. A knowledge of the above normal ranges and variations of the pituitary gland and its surrounding structures is important in diagnosing sellar and parasellar lesions.

Adolescent↗

Pattern and localisation of expression of vascular endothelial growth factor and its receptor flt-1 in the ovine pituitary gland: expression is independent of hypothalamic control.

The pituitary gland, a highly vascularised endocrine organ, contains permeable fenestrated endothelium that allows direct access of endocrine cells to the hemal milieu. Vascular endothelial growth factor (VEGF) has a mitogenic effect on endothelial cells and renders the endothelium more permeable. The following study investigated the expression of VEGF and its receptor flt-1 mRNA and protein in the pituitary gland of sheep. VEGF expression was localised, by in situ hybridisation and immunocytochemistry, mainly to the pars tuberalis/zona tuberalis (PT/ZT) region of the gland. No hybridisation signal was observed in the pars intermedia or pars nervosa. Reverse transcriptase-polymerase chain reaction (RT-PCR) Southern blotting confirmed the predominant expression of VEGF in the PT/ZT compared with the pars distalis (PD). Western blot analysis with the VEGF antibody revealed major (48 kDa) and minor (24 kDa) bands representing the monomer and dimer forms of VEGF and also confirmed the differential expression of VEGF in the PT/ZT compared with the PD. Double immunocytochemistry with VEGF and prolactin or luteinising hormone-beta (LH-beta) antibodies demonstrated that the VEGF-secreting cells are not lactotrophs or gonadotrophs. However, co-localisation of VEGF with S-100 was observed in a proportion of cells suggesting that some VEGF secreting cells are follicular stellate. Immunocytochemistry with a flt-1 antibody confirmed the expression of this high affinity receptor for VEGF in endothelial cells across the pituitary gland. Immunocytochemistry with the VEGF antibody using pituitary glands from intact and hypothalamo-pituitary disconnected sheep demonstrated comparable expression patterns suggesting that the regulation of blood flow and vascular permeability in the pituitary gland is under local regulation and is independent of hypothalamic input.

Animals↗

Fetal development of the pituitary gland in the beagle.

BACKGROUND: The pituitary gland of the dog is different from all animals and is described as "typical" for mammals. How might this complex pituitary gland of the dog be formed in fetal life? The current study examined the fetal development of the complex and unique dog pituitary and the ontogeny of specific cell types in the pars distalis. METHODS: Adenohypophysis of the beagle, from 25 to 60 days of gestation and at 2 days of age, was studied by immunocytochemical and histological staining. RESULTS: At 25 days gestation, the primordium (Rathke's pouch) of the adenohypophysis began to form by an upward evagination from the epithelium of the primary oral cavity. At 38 days, the pituitary gland showed the same morphology as in adult dogs, being merely smaller. Five walls of Rathke's pouch (anterior wall [A], lateral walls [L], posterior wall [P], and upper wall [U] were found at 25 days, and by 38 days they had specialized into specific regions of the adenohypophysis through complex and unique processes. The pars intermedia was derived from the U and the dorsal area of the A. The pars tuberalis was derived from the dorsal area of the A. The pars distalis was formed by more singular processes: the peripheral areas of the pars distalis were first formed by A and P; then the ventral lumen of the extensive Rathke's lumen surrounded by these areas was filled up by proliferation of cells, although the dorsal lumen remains as Rathke's lumen after 38 days. The blood capillaries may play an important role in the development of parencymal cells in the Rathke's pouch during canine fetal life. At 30 days gestation, the first adrenocorticotropic hormone cells were found in the anterior- and posterior-ventral regions (derived from middle and ventral areas of the A and the P) of the pars distalis anlage, and blood capillaries invaded the parenchymal cells from the mesencyme surrounding the anlage. At 38 days, portal vessels without capillary loops in the median eminence had appeared, and growth hormone and luteinizing hormone cells appeared in the ventral areas of A and P in the pars distalis. By 52 days, when capillary loops were seen in the portal vessels in the median eminence, these types of cells spread through the whole pars distalis. CONCLUSION: These areas in the epithelium of Rathke's pouch at 25 days may differentiate into specific regions of the pars distalis during subsequent fetal life, through complex processes that are characteristics to the canine species.

Adrenal Glands↗

Long-term organ culture of rat anterior pituitary glands.

An organ culture system for neonatal rat anterior pituitary glands has been developed in which cellular integrity and responsiveness to LH releasing hormone (LHRH) are maintained for at least 4 days. Anterior pituitary glands from Sprague-Dawley rats were cultured individually at 37 C in an atmosphere of 95% O2-5% CO2 in BGJb culture medium, Fitton-Jackson modification. Histological examination of 5-day-old rat pituitary glands cultured for 96 h in control medium revealed no evidence of tissue necrosis. By contrast, 40-day-old-rat anterior pituitary glands were centrally necrotic after only 24 h of incubation under the same conditions. The neonatal glands were treated for 24 h with synthetic LHRH, and medium and pituitary LH FSH concentrations were determined by double antibody radioimmunoassay. On the first day of culture, LHRH caused a dose-related release of LH with the minimal effective dose between 10(-10) and 10(-9)M. Near-maximal release appeared to be attained with 10(-6)M LHRH, which induced a 12-fold elevation in medium LH over controls. Release was evident within 3 h following stimulation with 10(-9)M LHRH. Pituitary glands were responsive to this dose at 0,24 and 72 h of culture with progressively increasing ratios between LHRH-stimulated and control LH levels of 3,13, and 24, respectively. Although FSH release by LHRH was not observed on the first day of culture, on the second day LHRH caused a dose-related secretion of this hormone. Specificity of the pituitary response was demonstrated for LH and TSH release following addition of LHRH and thyrotropin releasing hormone (TRH). The simplicity, sensitivity, reproducibility, and long-term viability of this neonatal rat anterior pituitary organ culture system make it a valuable technique for the study of gonadotropin secretion.

Age Factors↗

CT of the normal pituitary gland.

Retrospective evaluation of the pituitary gland on coronal post-contrast CT scan in 251 patients demonstrated that the pituitary gland is somewhat larger in females than in males. In males, glands measuring greater than 7.7 mm should be considered abnormal; in females, a statistically significant decline of gland height occurs with increasing age, the upper limit of normal for female gland height decreasing from 9.2 cm for a 20-year-old to 6.0 cm for a 90-year-old. Focal low densities greater than 3 mm are rare in males and probably should be considered abnormal.

Adolescent↗

Three-dimensional analysis of the developing pituitary gland in the mouse.

Prenatal development of the mouse pituitary gland was analyzed in three-dimensions by using confocal laser-scanning microscopy. In any wholemount preparation of the fetal pituitary gland from day 10 to day 18, immunofluorescence of laminin was observed in the deeper regions of the organ and demarcated the boundary of the epithelial tissue from the surrounding mesenchyme. Three-dimensional capillary networks in the fetal pituitary gland at day 13, day 15, and day 18 were visualized clearly by perfusing the blood vessels with an fluorescein isothiocyanate-labelled gelatin solution. During days 12-14, cellular plates protruded from the anterior wall of the pituitary anlage and extended toward the base of the infundibulum. At the same time, the mesenchyme situated among the cellular plates separated from the surrounding mesenchyme except at the anteroventral portion of the anlage. In a posterior wall of the anlage, intercellular depositions of laminin were found among the epithelial cells, some of which reached the laminin sheet in the basement membrane of the anlage. From days 15-18, the pituitary gland enlarged, and the mesenchyme spread radially from the median anteroventral portion to the lateral, posterior, and dorsal regions and finally expanded throughout the entire organ. At the periphery, the mesenchyme in the pituitary gland connected with that surrounding the capsule. Laminin was still found in the intercellular spaces between the epithelial cells, and most of the intercellular depositions of laminin were combined with the laminin sheet in the epithelial basement membrane. An abundance of vessels entered the organ from its anteroventral portion, spread, and connected with one another throughout the gland, similar to the distribution of mesenchyme. Intercellular laminin would induce the polarization of the contacting epithelial cells, resulting in rearrangement of the epithelial cells. The mesenchyme might spread in the pituitary gland, providing the intercellular laminin a foothold, in order to cleave the epithelial cell mass into lobules. The development of capillary nets in the adenohypophysis corresponded well with that of the mesenchyme. Because laminin localizes mainly in the basement membrane in the fetal organs, immunostaining of laminin clearly indicates the boundary between epithelial tissue and the mesenchyme. Three-dimensional observation of laminin in wholemount preparation is very useful for studying morphogenesis.

Animals↗

Isolation and biochemical study of secretory granules from rat pituitary glands.

Secretory granules from anterior pituitary glands of young adult male castrate rats were isolated by differential centrifugation, microfiltration, and discontinuous density gradient centrifugation. The granules were obtained as pellets, sectioned, and studied with the electron microscope. A major part of the gonadotropin and a substantial amount of the TSH were associated with the isolated granules. Negligible amounts of growth hormone and prolactin were present as contaminants. Succinic dehydrogenase, glucose-6-phosphatase, acid protease, and acid and alkaline phosphatases were not found in the granules. Alkaline protease was the only enzyme found to be associated with the granules, and it is suggested, in the light of these results, that the alkaline protease may be involved in the release of the hormones.

Animals↗

Histological changes in the pituitary gland and adenomas following radiotherapy.

To elucidate histological changes in the pituitary gland and adenomas following radiotherapy, two irradiated pituitary glands and seven irradiated non-functioning adenomas were studied. The latter included four cases with conventional radiation (CR) and three cases with radiosurgery: two with gamma knife radiosurgery (GKR) and one with stereotactic fractionated radiotherapy (SRT). The specimens were obtained 10 months to 10 years (mean 58 months) after the radiotherapy. Irradiated pituitary glands showed diffuse fibrosis in the adenohypophysis, whereas irradiated adenomas showed either mild or no fibrosis in five CR/SRT cases and diffuse thick hyaline deposits in two GKR cases. No necrosis was observed. Stellate-shaped S-100 protein-positive cells were greater in number in the irradiated pituitary glands than in the normal glands. Pituitary cells with dense granular reactivity for mitochondrial protein, cytochrome oxidase, and Mn-SOD, mimicking oncocytes, were greater in number in the irradiated adenohypophysis but did not show any change in cell size. Many irradiated pituitary cells and some irradiated adenoma cells were densely positive with anticytokeratin 1,5,10,14 antibody whereas non-irradiated counterparts were negative. In adenomas, MIB-1 labeling index remained unchanged after the radiation. The results may indicate that radiation-induced fibrosis was associated with an increased number of folliculo-stellate cells, mitochondrial dysfunction, and squamous metaplasia. These findings were prominent in irradiated pituitary cells and may participate in delayed pituitary hypofunction following radiotherapy. In irradiated adenoma cells, similar findings were observed but diffuse fibrosis was absent. The histological changes were more intensive in adenomas following GKR than those following CR.

Adenoma↗

Release of endogenous 5-hydroxytryptamine from the neural and the intermediate lobe of the rat pituitary gland evoked by electrical stimulation of the pituitary stalk.

A calcium-dependent release of 5-hydroxytryptamine from the neural and intermediate lobe of the rat pituitary gland has been demonstrated following electrical stimulation of the pituitary stalk with stimulation parameters thought to evoke propagated action potentials. The 5-hydroxytryptamine release from the intermediate lobe was double that from the neural lobe. The mass of the intermediate lobe of the rat is about 80% of that of the neural lobe [Holzbauer, Racké, Mann, Cooper, Cohen, Krause and Sharman (1984) J. Neural Transm. 59, 91-104]. The relatively high overflow of 5-hydroxytryptamine from the intermediate lobe agrees with immunohistochemical studies in which a larger number of 5-hydroxytryptamine fibres were seen in the intermediate lobe than in the neural lobe. The present results have demonstrated that the rat hypophysis contains neuronal 5-hydroxytryptamine. They also suggest that this amine may act as a neurotransmitter substance in the neural and intermediate lobe.

Animals↗