Showing papers on "Hypophysectomy published in 2001"

Microarray analysis of the in vivo effects of hypophysectomy and growth hormone treatment on gene expression in the rat.

Abstract: Complementary DNA microarrays containing 3000 different rat genes were used to study the consequences of severe hormonal deficiency (hypophysectomy) on the gene expression patterns in heart, liver, and kidney. Hybridization signals were seen from a majority of the arrayed complementary DNAs; nonetheless, tissue-specific expression patterns could be delineated. Hypophysectomy affected the expression of genes involved in a variety of cellular functions. Between 16-29% of the detected transcripts from each tissue changed expression level as a reaction to this condition. Chronic treatment of hypophysectomized animals with human GH also caused significant changes in gene expression patterns. The study confirms previous knowledge concerning certain gene expression changes in the above-mentioned situations and provides new information regarding hypophysectomy and chronic human GH effects in the rat. Furthermore, we have identified several new genes that respond to GH treatment. Our results represent a first step toward a more global understanding of gene expression changes in states of hormonal deficiency.

Transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in 7 cats.

Abstract: Methods— Urinary cortisol/creatinine ratios, pituitary-adrenocortical function tests, and computed tomography (CT) were performed on 7 cats that presented with a provisional diagnosis of hyperadrenocorticism. All cats underwent microsurgical transsphenoidal hypophysectomy with histologic examination of the excised specimen. Follow-up consisted of clinical evaluation, repeat adrenocortical function testing, and CT. Results— Four cats had concurrent diabetes mellitus. In all cats, the urinary cortisol/creatinine (C/C) ratios were elevated. The dexamethasone screening test showed that 2 cats did not meet the criterion for hyperadrenocorticism. The response of the cats’ plasma concentrations of cortisol and adrenocorticotrophic hormone to a high dose of dexamethasone varied from very sensitive to completely dexamethasone resistant. Basal plasma a-melanocyte‐stimulating hormone concentrations were elevated in 2 cats with a pars intermedia adenoma and in 3 cats with an adenoma that originated from the anterior lobe. Preoperative CT enabled accurate assessment of pituitary size (5 nonenlarged pituitaries with a height ,4 mm and 2 enlarged pituitaries with a height .5 mm) and localization relative to intraoperative anatomic landmarks. Two cats died within 4 weeks after surgery of a nonrelated disease. In the remaining 5 cats, the hyperadrenocorticism went into both clinical and biochemical remission. Hyperadrenocorticism recurred in 1 cat after 19 months, but no other therapy was given and the cat died at home 28 months after surgery. CT evaluation of this cat had identified pituitary remnants 6 weeks after surgery. The main postoperative complications were oronasal fistula (1 cat), complete dehiscence of the soft palate (1 cat), and transient reduction of tear production (1 cat). One cat died at 6 months (undefined anemia), and another cat at 8 months (recurrent nose and middle ear infection secondary to soft palate dehiscence) after surgery. In the surviving 2 cats, the remission periods at the time of writing were 46 and 15 months. In the 2 cats with sufficient follow-up time, the concurrent diabetes mellitus disappeared, ie, insulin treatment could be discontinued at 4 weeks and 5 months after hypophysectomy. In all 7 cats, the histologic diagnosis was pituitary adenoma. Conclusions— Microsurgical transsphenoidal hypophysectomy is an effective method of treatment for feline PDH in specialized veterinary institutions having access to advanced pituitary imaging techniques. Concurrent diabetes mellitus is usually reversible after hypophysectomy. Thorough presurgical screening for coexisting diseases is imperative.

Hypophysectomy as a treatment for canine and feline Cushing's disease.

Abstract: The microsurgical technique of transsphenoidal hypophysectomy performed with the dogs and cats positioned in sternal recumbency enables the treatment of Cushing's disease, independent of skull type, in a safe and effective manner. In dogs, the short-term survival rate after hypophysectomy is comparable to that after treatment with o,p'-DDD, whereas the recurrence rate in this period is lower. When the surgeon has gone through a learning curve, the results of the 1- to 3-year follow-up interval may be better than those after adrenocorticolysis with o,p'-DDD. CT enables assessment of localization and size of the pituitary before surgery. In general, dogs with Cushing's disease and normal-sized pituitaries or moderately enlarged pituitaries (up to 12 mm in diameter) are suitable candidates for transsphenoidal surgery. In dogs with larger pituitary tumors and tumor extension rostrally or caudally over the dorsum sellae, transsphenoidal debulking surgery may be only a palliative treatment. The main complications are postoperative hypernatremia, keratoconjunctivitis sicca, diabetes insipidus, and secondary hypothyroidism. In cats, special attention should be paid to closure of the soft palate. The neurosurgeon must be familiar with these complications so as to recognize them as early as possible and to treat them immediately and effectively. It is concluded that microsurgical transsphenoidal hypophysectomy in dogs and cats with Cushing's disease is an effective method of treatment.

The role of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins essential for adrenal steroidogenesis in the late-gestation ovine fetus.

Abstract: To further understand the relative roles of the pituitary gland and ACTH in the regulation of mRNAs encoding proteins that are essential for adrenal development, we investigated the effects of, first, an ACTH infusion and labour in intact fetuses and, secondly, the effect of an ACTH infusion to fetuses with and without a pituitary gland, on the relative abundance of the mRNA encoding for the ACTH receptor (MC2R), steroidogenic factor 1 (SF-1), cholesterol side-chain cleavage enzyme (P450(scc)), 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17alpha-hydroxylase (P450(C17)) in the fetal adrenal gland. ACTH(1-24) infusion (14.7 pmol/kg per h) to intact fetuses was without effect on the abundance of mRNA encoding MC2R and SF-1, irrespective of whether the infusion was given for 18 (115-132 days of gestation) or 32 days (115 days to term (147 days of gestation)). Hypophysectomy (HX) did not alter the expression of MC2R mRNA; however, the abundance of SF-1 mRNA fell by approximately 50% following the removal of the pituitary gland. ACTH(1-24) infusion to HX fetuses failed to restore levels of SF-1 mRNA to that seen in intact animals. P450(scc) and 3betaHSD mRNAs were increased by ACTH(1-24) infusion for 18 days in intact animals, although no effects of the infusion were seen on P450(C17) mRNA levels. For all three of these mRNAs, there was a significant increase in their abundance between 132 days of gestation and term in intact fetuses. By term, ACTH(1-24) infusion was without any additional effect on their abundance. HX decreased the expression of P450(scc), 3betaHSD and P450(C17) mRNAs, while ACTH(1-24) infusion to HX fetuses increased the expression of these mRNAs to levels seen in intact animals. There were significant correlations between the abundance of the mRNA for P450(scc), 3betaHSD and P450(C17), but not MC2R and SF-1, and premortem plasma cortisol concentrations. These results emphasise the importance of the pituitary gland and ACTH in the regulation of the enzymes involved in adrenal steroidogenesis. Factors in addition to ACTH may also play some role, as the infusion was not always effective in increasing the abundance of the mRNAs. Surprisingly, the mRNA for MC2R and SF-1 did not appear to be regulated by ACTH in the late-gestation ovine fetus, though a pituitary-dependent factor may be involved in the regulation of SF-1 mRNA abundance.

A Novel Approach to Reducing Postoperative Intraperitoneal Adhesions Through the Inhibition of Insulinlike Growth Factor I Activity

Abstract: Hypothesis Interference with insulinlike growth factor I (IGF-I) activity, both systemically and intraperitoneally, reduces postoperative intraperitoneal adhesion severity. Setting Experimental animal model. Design, Interventions, and Main Outcome Measures: Adult female rats were subjected to hypophysectomy, sham hypophysectomy (control), IGF binding protein 4 (IGFBP-4) treatment, or albumin treatment (control). All rats underwent laparotomy and uterine horn abrasion with adjacent parietal peritoneal trauma for the purpose of creating postoperative intraperitoneal adhesions. Glucocorticoids and thyroid hormone were replaced in the hypophysectomy group. On postoperative day 10, rats were weighed, subjected to phlebotomy, and killed. Postmortem laparotomies were performed and blinded observers scored uterine-peritoneal adhesions on a 0 to 3 scoring system. Plasma IGFBP-4 levels and organ weights were measured in the IGFBP-4 and albu-min treatment groups. Blood samples in all rats were analyzed for IGF-I levels. Results Rats with low IGF-I levels (hypophysectomy) and inhibited IGF-I activity (IGFBP-4 treatment) formed significantly less severe adhesions than their control counterparts. As expected, rats in the hypophysectomy group displayed greater weight loss and lower plasma IGF-I levels than sham-treated rats. Rats treated with IGFBP-4 and those treated with albumin demonstrated no differences in body weight, organ weights, IGF-I levels, and IGFBP-4 levels. Conclusions Both the reduction of systemic IGF-I levels via hypophysectomy and the inhibition of local intraperitoneal IGF-I activity via IGFBP-4 treatment resulted in diminished postoperative adhesion severity. Treatment with IGFBP-4 may play a role in postoperative adhesion prophylaxis in the future.

The hypophysis controls expression of SNAP-25 and other SNAREs in the adrenal gland.

Abstract: SNAP-25 (Synaptosomal Associated Protein of 25 kDa), in association with two other SNARE (soluble NSF attachment protein receptor) proteins, syntaxin and Vesicle Associated Membrane Protein, VAMP, is implicated in regulated and constitutive exocytosis in neurones and neuroendocrine cells. Our previous studies have shown that it is expressed more by noradrenergic than adrenergic chromaffin cells in the rat adrenal gland. Since certain hormones under hypophyseal control play an essential role in determining chromaffin cell phenotype, the present study examined the effect of hypophysectomy on SNAP-25 expression. Hypophysectomy was found by immunoblotting and RT-PCR analysis to increase adrenal gland SNAP-25, syntaxin-1 and VAMP-2 levels, without modifying the relative expression of SNAP-25 isoforms: immunocytochemistry showed a dramatic increase in SNAP-25 expression in former adrenergic chromaffin cells. Since adrenal glucocorticoids are considerably reduced by hypophysectomy, the effect of corticosterone replacement therapy was investigated. This did not change levels of SNAP-25, syntaxin-1 or VAMP-2. SNARE expression was also unmodified in pheochromocytoma cells treated with a synthetic glucocorticoid. In contrast, subcutaneous injection of hypophysectomized rats with thyroid hormone decreased adrenal SNAP-25, demonstrating the potential importance of the pituitary-thyroid axis. The current data thus demonstrate that the hypophysis exerts an inhibitory control on adrenal gland SNARE proteins. They suggest that glucocorticoids are unlikely to be directly responsible for this but provide evidence that thyroid hormones are implicated in this phenomenon. The putative role of hormonal regulation on SNARE function is discussed.

[Transsphenoidal hypophysectomy of a patient with an ACTH-producing pituitary adenoma and an "empty sella" after pretreatment with etomidate].

Abstract: HISTORY AND ADMISSION FINDINGS: A seventy-year-old woman was admitted to our hospital under suspicion of an adrenal Cushings's syndrome. Initial laboratory values showed elevated cortisol (834 nmol/l; normal: 180-640) which could not be suppressed after administration of 2 mg dexamethasone (632 nmol/l). Computed tomography of the abdomen showed a 19 x 34 mm mass in the region of the left adrenal gland. INVESTIGATIONS: ACTH levels were normal (42 ng/ml; 17-52). Serum cortisol remained high at 1021 nmol/l after administration of 8 mg dexamethasone. Four more doses of 2 mg dexamethasone were applied on 3 consecutive days, leading to a mild suppression of serum cortisol to 705 nmol/l, with urine cortisol levels dropping from 1915 to 101 nmol/l/24 h. The CRH-test produced a rise of serum cortisol from 895 to 1475 nmol, with ACTH rising from 42 to 68 pg/ml, a laboratory constellation consistent with the diagnosis of centrally located Cushing's syndrome (Cushing's disease). MRI failed to show an adenoma of the pituitary gland so that sinus petrosus sampling was done to confirm the diagnosis (ACTH central/peripheral 7:1; normal range < 2:1). TREATMENT AND COURSE: Serum cortisol rose to 1070 nmol/l and the patient developed pneumonia and contracted tinea. Prior to surgery we lowered the excessive cortisol levels with etomidate and successfully treated the pneumonia with antibiotics. Postoperatively clinical symptoms of Cushing's syndrome disappeared. The patient now presented with total insufficiency of the anterior pituitary. CONCLUSION: Exact hormone testing that may involve sinus petrosus sampling is necessary in diagnosing Cushing's syndrome. Even if radiological procedures cannot show an adenoma of the pituitary, transsphenoidal resection should be considered. Etomidate can lower excessive cortisol levels in seriously ill patients.

Characterization of GFAP expression and cell proliferation in the rat median eminence following hypophysectomy.

Abstract: To analyze whether the reorganization of the rat median eminence after hypophysectomy might be related to changes in glial fibrillary acidic protein (GFAP)- and cellular proliferation, the distribution of cells immunoreactive for GFAP and the proliferation rate of such cells were analyzed at 20, 40 and 60 days posthypophysectomy. For this study, four rostro-caudal regions of the median eminence were differentiated: the retrochiasmatic, preinfundibular, infundibular and postinfundibular regions. In each of these regions, three layers were studied: the ependymal, the internal and the external. At 20 and 40 days after hypophysectomy, significant increases in cellular proliferation affecting all three layers studied in the preinfundibular and infundibular regions were found. At the same time points, increases in GFAP expression were also observed. However, after 60 days, GFAP and proliferative cellular nuclear antigen (PCNA) expression decreased. Although variations of PCNA and GFAP levels were evident, no colocalisation of PCNA and GFAP was found in the cells of the median eminence in untreated or hypophysectomized rats when sections were analyzed by double immunohistochemical staining. Our results suggest that reorganization of median eminence involves alterations (or modulation) of GFAPimmunoreactive cells together with a proliferation of cells that are not GFAP-immunoreactive. This study also demonstrates that this reorganization is completed within the first two months after hypophysectomy.

Apoplexy in a recurrent pituitary adenoma.

Abstract: A 75 year old woman, with a history of trans-sphenoidal hypophysectomy for a non-secreting pituitary adenoma 15 years ago and currently on glucocorticoid and thyroid hormone replacement, was found unconscious on …

[History of pituitary surgery in humans and animals: from experiments with dogs to treatment of patients].

Abstract: At the end of the 19th century and the start of the 20th century experimental hypophysectomy was carried out on cats and dogs, by means of the lateral temporal approach, to investigate the physiological role of the pituitary gland because there was a debate as to whether the pituitary gland was essential for life. At the same time pioneering neurosurgeons such as Harvey Cushing used animal experiments to explore the different approaches to the neurocranium and the pituitary, thereby taking the first steps towards neurosurgery in humans. Eventually the transsphenoidal route was chosen for such an operation. Veterinary medicine has benefited from these developments in the medical field. For the past few decades, hypophysectomy has been used for the treatment of pituitary adenomas in dogs and cats that are kept as pets.

Fertility in Hypophysectomized Pituitary Grafting: Part i Function and·

Abstract: Male rats underwent hypophysectomy and graft procedures, and a normal control group (C) was also established. In the hypophysectomy-plus-pituitary graft (HC) group, a suspension of neonatal rat pituitary cells (cortical ce lls in the hypophysectomy-plus-cortical graft (CC) group) was implanted into the third ventride. Four weeks later, the surviving hypophysectomy only H (n=21), HC (n=21), and CC (n=21) rats were evaluated for copulation/ ejaculation/ fertility. Endocrine target organs were histologically examined, and serum levels of luteinising hormone (LH) and testosterone were compared among the four groups. LH response to endogenous (cold stress) and exogenous (gonadotropin-releasing hormone injection) stimuli was also assessed in the experimental groups. The HC group had higher LH than the H and CC groups (0.89 ± 0.2 pg/ml versus 0.58 ± 0.2 pg/ml and 0.47 ± 0.3 pg/ml, respectively; p<0.05), but lower LH than controls (p<0.05). The LH response to exogenous and endogenous stimuli was greater in the HC than in the H and CC rats (p<0.05). Only control rats had detectable testosterone. HC rats (52.4%) were more sexuallyactive than H (5.3%) and CC (5.5%) animals (p