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Laparoscopic bilateral adrenalectomy following failed hypophysectomy.

BACKGROUND: Laparoscopic adrenalectomy has recently been shown to be a safe and effective means of treating adrenal pathology with much lower morbidity than the traditional approach. The majority of reports in the literature involve removal of adrenal tumors. Although open bilateral adrenalectomy has been utilized for persistent Cushing's syndrome following attempted hypophysectomy, there is little data available describing the application of laparoscopic adrenal surgery to this problem. METHODS: Four patients with persistent Cushing's syndrome after attempted treatment with hypophysectomy underwent laparoscopic bilateral adrenalectomy at our institution. One procedure was done transabdominally in the supine position. Three procedures were done transabdominally using sequential lateral decubitus positions. RESULTS: All procedures were completed laparoscopically. The mean operative time was 4.6 h (range 3.9-5.25). Repositioning and reprepping the patients resulted in a slight increase in operative time, but visualization was improved using the lateral decubitus position. Average blood loss: 156 cc (range 50-300). One patient required early reoperation for bleeding from the left adrenal bed, which was controlled laparoscopically. Three patients were eating the following day and were discharged on postoperative days 1, 2, and 5. The fourth patient remained hospitalized for 18 days due to problems unrelated to surgery. After a mean follow-up of 10 months, all patients have done well and have no clinical or biochemical evidence of recurrent disease. CONCLUSION: Our clinical experience indicates that laparoscopic bilateral adrenalectomy is a viable treatment option for Cushing's syndrome following failed hypophysectomy.

Adrenalectomy↗

Meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy.

Following hypophysectomy the regenerating fibers of magnocellular neurons are known to establish new neurohemal connections with reorganized vasculatures in the median eminence, which lead to establishment of a posterior pituitary-like structure. In order to examine the role of the meninges (the pia mater and the arachnoid) in this regeneration process, we implanted the meningeal tissues obtained from neonatal rat pups into the third ventricle of the adult rats, and then hypophysectomized the host animals. Ten days after hypophysectomy, the meningeal tissue grafts were found to be densely innervated by regenerating vasopressin-immunoreactive fibers. Such fibers had dots and frequently formed large punctuations. On the contrary, few vasopressin fibers were found within the cortical tissue grafts. Further, the exposure of primary hypothalamic cell cultures to the medium conditioned by meningeal cell cultures promoted not only the survival of vasopressin-immunoreactive neurons but also the outgrowth and aborization of the neurites. The survivals of cortical and cerebellum neurons in culture were also promoted by the conditioned medium. These findings raise the possibility that the meninges play an important role in the axonal regeneration process after hypophysectomy.

Animals↗

Hypophysectomy fails to affect the supersensitivity of striatal dopamine target cells induced by prolonged haloperidol treatment.

The influence of hypophysectomy on biochemical indices of striatal dopamine target cell supersensitivity induced by prolonged haloperidol treatment was investigated in the rat. Hypophysectomy itself did not modify dihydroxyphenylacetic acid (DOPAC) levels but slightly enhanced acetylcholine concentrations in the striatum. Hypophysectomy failed to affect the ability of haloperidol, apomorphine and pergolide to alter these biochemical parameters after acute administration. Prolonged administration of haloperidol (by means of osmotic minipumps delivering 2.5 micrograms/h) for 14 days caused a decrease in DOPAC and an increase in acetylcholine levels in the striatum during withdrawal; these effects were of a similar magnitude in sham-operated and hypophysectomized rats. Moreover, there was a similar degree of tolerance to the elevation of DOPAC and to the diminution of acetylcholine concentrations in striatum in response to challenge with haloperidol during withdrawal in sham-operated and hypophysectomized animals. Finally, a similar supersensitive biochemical response to pergolide (decrease in DOPAC and increase in acetylcholine levels) was observed in both hypophysectomized and sham-operated animals after prolonged haloperidol treatment. These data suggest that hypophyseal factors do not affect the development of striatal dopamine target cell supersensitivity caused by prolonged haloperidol treatment.

Acetylcholine↗

Effects of fasting, pancreatectomy, and hypophysectomy in the yellow eel, Anguilla rostrata.

Metabolic effects of pancreatectomy and hypophysectomy are investigated in the yellow American eel, Anguilla rostrata, fasted for 6 months. The results are compared with the findings in freshly captured eels subjected to the same operations. In intact animals, fasting causes a statistically significant decrease in serum amino acid nitrogen (AAN), serum urea, and relative liver weight, and an increase in serum free fatty acids (FFA), serum cholesterol, and tissue hydration. Serum glucose, liver and muscle glycogen, liver and muscle fatty acids, and abdominal fat stores do not show significant alterations. The absence of diabetes mellitus after pancreatectomy, seen in previous studies, is confirmed. However, pancreatectomy affects fewer parameters in fasting eels than in fed ones. After hypophysectomy, the situation is similar; only serum AAN shows an impact of the operation in fasted eels. As in freshly captured eels, surgical stress seems to affect almost all metabolic parameters. It appears that the smaller impact of both pancreatectomy and hypophysectomy in fasted eels reflects the reduced role of hormones in the state of lowered metabolism.

Amino Acids↗

Effects of hypophysectomy and substitution with growth hormone, prolactin, and thyroxine on growth and deposition in juvenile frogs, Xenopus laevis.

Growth was studied in young metamorphosed frogs, Xenopus laevis, following hypophysectomy and substitution with mammalian growth hormone (bGH or pGH), mammalian prolactin (oPRL), and thyroxine. Hypophysectomy reduced growth (weight and length increase). GH and PRL proved equally efficient in restoring growth and in mobilizing energy stores (fat bodies and liver glycogen). No synergistic effects between GH and PRL could be observed. GH exerted its growth-promoting effects by increasing gross food conversion efficiency (weight increase/food intake), but did not stimulate appetite. Moderate GH doses given to a group of frogs in growth stagnation exerted moderate metabolic effects, and may have stimulated appetite in some animals, but did not increase body size significantly. Thyroxine was unable to promote growth, but increased mobilization of energy stores. Hypophysectomy and hormone substitution affected feeding behavior. The nature of the actions of pituitary somatotropic hormones and of thyroxine on growth and deposition is discussed.

Animals↗

Effects of hypophysectomy and subsequent hormonal replacement therapy on hormonal and osmoregulatory status of coho salmon, Oncorhynchus kisutch.

This study investigates the effects of hypophysectomy and subsequent hormone replacement therapy upon the hormonal and osmoregulatory status of coho salmon, Oncorhynchus kisutch, in 7% seawater (SW) and SW. Following hypophysectomy, coho salmon were injected every 2 days for 8 days with thyroxine, growth hormone, and cortisol, alone or in combinations, and sampled 2 days after the final injection. Increased environmental salinity raises plasma sodium, calcium, and magnesium levels, as well as plasma osmolality. Cortisol is hypercalcemic and thyroxine is hypocalcemic in hypophysectomized salmon, but it is unclear whether these effects are due directly to calcium regulation or are the consequence of general effects on the plasma osmotic/ionic balance. Growth hormone and thyroxine together, but not separately, decrease and increase magnesium levels, at low and high environmental salinities, respectively, indicating a complex endocrine control of plasma magnesium. Gill Na+, K+-ATPase activity in hypophysectomized salmon is stimulated by growth hormone and cortisol, but inhibited by thyroxine and raised environmental salinity. This implies a complex endocrine control and indicates that hormonal support is needed to sustain or raise gill Na+, K+-ATPase activity in seawater. Increased environmental salinity induces elevation of plasma cortisol levels in apparent absence of pituitary control, indicating that the interrenals may respond to changes in external and/or internal environment, either directly or indirectly through extrapituitary hormonal or nervous control. Cortisol is a potent inhibitor of calcitonin secretion, as seen by the large decrease in plasma calcitonin levels in cortisol-treated hypophysectomized fish. The study was carried out at a time when thyroxine plasma levels were low. These basal levels were not affected by hypophysectomy, possibly indicating a basal release of thyroxine from the thyroid without stimulatory support of the pituitary gland.

Animals↗

The effect of hyper and hypothyroidism, hypophysectomy and adrenalectomy on phosphatidylethanolamine methyltransferase, phosphatidyldimethyl-ethanolamine methyltransferase and choline phosphotransferase of rat liver microsomes.

The effect of hyper- and hypothyroid, hypophysectomy and adrenalectomy on phosphatidylcholine biosynthetic enzymes, phosphatidylethanolamine methyltransferase, phosphatidyldimethylethanolamine methyltransferase and choline phosphotransferase of liver microsomes was measured in rats. There was a significant increase in the specific activity of phosphatidylethanolamine methyltransferase in the hyperthyroid rats. There was a significant reduction in the specific activity of phosphatidylethanolamine methyltransferase and phosphatidyldimethylethanolamine methyltransferase in the hypothyroid states. The choline phosphotransferase increased significantly in the hyperthyroid state and decreased in the hypothyroid animals. Hypophysectomy resulted in a significant increase in specific activity of choline phosphotransferase. A reduction in the specific activity of the phosphatidylethanolamine methyltransferase occurred after 28 days of hypophysectomy. Adrenalectomy resulted in a significant stimulation of the specific activity of phosphatidylethanolamine methyltransferase and choline phosphotransferase in liver microsomes.

Adrenalectomy↗

Effects of hypophysectomy and immobilization stress on S-adenosylmethionine levels in rat adrenal glands.

Rat adrenal S-adenosylmethionine (SAM) levels and phenylethanolamine-N-methyltransferase (PNMT) activity were measured under conditions of hypophysectomy and stress. A new dual-label radioenzymatic assay for SAM is presented which eliminates problems found to exist with previous methods. Strain-specific differences in both PNMT and SAM were found, as well as sex differences in SAM levels. Immobilization stress resulted in an increase in adrenal SAM and PNMT activity, while hypophysectomy decreased both. The distribution of SAM between cortex and medulla did not change with either hypophysectomy or stress. Hypophysectomized Fisher rats were found to be capable of increasing PNMT activity in the absence of increased SAM levels.

Adrenal Glands↗

The effects of hypophysectomy and continuous food restriction, begun at ages 70 and 400 days, on collagen aging, proteinuria, incidence of pathology and longevity in the male rat.

Hypophysectomy in young male Wistar rats aged 70 days, followed by cortisone acetate replacement therapy throughout life, retarded the rate of aging of tail tendon collagen fibres, inhibited the development of certain diseases of old age (renal disease, cardiac enlargement, hind limb paralysis, and various endocrine and non-endocrine tumors) and significantly prolonged the duration of life. Almost identical anti-aging effects were obtained by lowering the food intake of intact rats to that of hypophysectomized rats, from age 70 days until death. Hypophysectomy in middle age, at 400 days, even with cortisone acetate replacement therapy, produced a sharp increase in the mortality rate; the surviving rats exhibited significantly reduced aging of collagen fibres and of the kidney as measured by protein excretion. Food restriction begun at 400 days also inhibited renal aging, but had no demonstrable effect on collagen aging during the first 100 days. These studies suggest that procedures such as hypophysectomy and food restriction do not switch off an aging mechanism in youth but probably exert a continuing inhibitory influence on certain aging processes throughout life.

Aging↗

Effect of hypophysectomy on schedule-induced wheelrunning.

Previous research has shown that adrenalectomy suppresses schedule-induced wheelrunning, and that the suppressant effect of adrenalectomy can be totally reversed by the replacement of corticosterone. The present study confirms the role of the hormones of the pituitary adrenocortical axis in the control of schedule-induced wheelrunning by means of hypophysectomy. As anticipated, hypophysectomy also suppressed schedule-induced wheelrunning. The suppressant effect of hypophysectomy on schedule-induced wheelrunning was partially, but significantly restored by the implantation of corticosterone. Present findings, in conjunction with the previous work, show that schedule-induced wheelrunning is markedly dependent on the function of the pituitary-adrenal axis, and the nature of pituitary-adrenal involvement is mainly through circulating corticosterone levels.

Animals↗

Thyroxine replacement after hypophysectomy alters the pattern of enkephalin localisation in the adrenal medulla of the fetal sheep.

It has been suggested that a pituitary-derived or -dependent factor may suppress enkephalin peptide synthesis in the central noradrenaline- containing cells of the sheep adrenal medulla in late gestation. We have investigated the effect of thyroxine (T4) replacement after fetal hypophysectomy on the localisation of enkephalin peptides within the peripheral adrenaline- and central noradrenaline-containing regions of the adrenal medulla of the fetal sheep. Fetal hypophysectomy (HX) was performed in 12 fetal sheep at 105-108 days gestation (term = 145 +/- 3 days gestation). T4 (40 micrograms/kg/24h) (HX + T4) or saline (HX + Sal) were infused between 110 and 140 days gestation. Adrenal glands were collected from the HX + T4, HX + Sal groups and from a group of intact fetal sheep (n = 4) for immunohistochemistry using anti- met-enkephalin and an avidin-biotin staining system. In adrenals from intact fetal sheep, there was intense positive staining for met-enkephalin in the peripheral adrenaline-containing region and sparse staining for enkephalins in the central noradrenaline-containing region. In contrast, in the HX + Sal group, enkephalin staining was uniformly present throughout the peripheral and central regions of the adrenal medulla. In the HX + T4 group, however, the staining density of met-enkephalin was higher within the adrenaline cells of the peripheral rim of the medulla than in the central medullary region. We have demonstrated that T4 replacement after fetal hypophysectomy restores the normal ontogenetic pattern of localisation of enkephalin peptides within the fetal adrenal. We postulate that T4 acts either indirectly via neural mechanisms or directly at the noradrenaline-containing cells to mediate the suppression of enkephalin staining within the central noradrenaline-containing region of the adrenal medulla of the fetal sheep in late gestation.

Adrenal Medulla↗

Inhibitory effect of hypophysectomy and food restriction on glomerular basement membrane thickening, proteinuria and renal enlargement in aging male Wistar rats.

Age-related thickening of the glomerular basement membrane (GBM) was studied in three groups of male Wistar rats: (a) ad libitum fed, (b) hypophysectomized and (c) food-restricted eating the same amount of food as hypophysectomized rats, but about 45% of the ad libitum fed group. Studies were begun at 50 days (2 months) and continued throughout life. Multiple regression was used to statistically assess the effects of age and treatments. In ad libitum fed male rats GBM thickness increased from 114 nm at 50 days (2 months) to 632 nm at 1,000 days (33 months). GBM thickness at 1,000 days was 296 nm in hypophysectomized rats and 392 nm in food restricted rats. Hypophysectomy had a significantly greater inhibitory action on GBM thickening than food restriction, in rats eating the same quantity of food per day. However, a major part of the effect of hypophysectomy may be due to the permanent fall in food intake (from 16.3 to 7.9 g/day) resulting from the operation. Accompanying the age-related thickening of the GBM in ad libitum fed rats were proteinuria and renal enlargement, both of which were inhibited by hypophysectomy and food restriction.

Aging↗

Effect of ovariectomy, hypophysectomy and/or GnRH analog (HRF) administration on the cell proliferation of the MXT mouse hormone-dependent mammary tumor.

The MXT tumor is an experimental mammary neoplasm which is maintained by serial transplantation using B6D2F1 mice, and which contains significant amounts of estrogen and progesterone receptors. The aim of the present study is to examine the effects of ovariectomy (OVX) or ovariectomy plus hypophysectomy (OVX-HX) on both the macroscopic growth and the cell proliferation of this tumor. This cell proliferation was evaluated by means of in vivo tritiated thymidine autoradiography. In addition, we investigated the effects of a GnRH analog (Gonadorelin: HRF, 5-oxo-Pro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-hydrochloride) on MTX tumor cell proliferation on 7 day-OVX and 5 day-HX (OVX-HX) mice. The uterine luminal epithelium was chosen to monitor the methodology. Our data clearly demonstrate that there is a delay in the growth of MXT tumors grafted into hypophysectomized animals and, to a lesser degree, ovariectomized animals. With respect to proliferation, castration induced a dramatic decrease of the thymidine labelling index (TLI) in the tissue used to monitor the methodology (the uterine luminal epithemium); in contrast, no cell proliferation was induced by hypophysectomy or HRF administration. In 4-week-old MXT tumors, ovariectomy also markedly decreased the TLI within a few days of its taking place. However hypophysectomy, performed on castrated animals, induced a significant and transient increase of cell proliferation in this neoplasm, an increase which lasted from the 2nd to the 5th day following the operation. The high basal level of MXT cell proliferation recorded in OVX-HX animals decreased dramatically after the administration of HRF between 12 and 48 h prior to the sacrifice of the animals. It is concluded that the HRF exerts a direct effect on the MXT tumor cells, and this HRF might be essential for their growth.

Animals↗

Effect of hypophysectomy on alpha-melanotropin in discrete regions of the rat brain.

The effect of hypophysectomy on alpha-melanotropin (alpha MSH) concentrations in discrete brain regions was investigated. Hypophysectomy resulted in a 38-69% decrease in alpha MSH concentration in alpha MSH terminal regions 4 weeks after surgery. In contrast, the alpha MSH concentration in the arcuate nucleus, site of alpha MSH containing perikary, was unaffected by hypophysectomy. These results indicate that the brain alpha MSH system is distinct from, but related to that of the pituitary.

Animals↗

Changes of vasopressin- and oxytocin-immunoreactive neurons after hypophysectomy in young and old mice.

Changes of magnocellular neurons after hypophysectomy were immunohistochemically studied using antisera to arginine vasopressin (AVP) and oxytocin (OXT) in young and old female mice of the C57BL/Tw strain. AVP-immunoreactive neurons in the supraoptic and paraventricular nuclei of intact 19-month-old mice showed a marked reduction in number and immunoreactivity as compared with those of intact 3-month-old mice. Age difference of OXT-immunoreactive neurons was less pronounced than that of AVP-immunoreactive neurons. After hypophysectomy, both AVP- and OXT-immunoreactive neurons showed an intense stainability 10 days after the operation regardless of ages. However, the rate of reduction in number of immunoreactive neurons after hypophysectomy was less marked in 19-month-old than 3-month-old mice.

Aging↗

Acute effects of hypophysectomy and administration of pancreatic and thyroid hormones on circulating concentrations of somatomedin-C in young chickens: relationship between growth hormone and somatomedin-C.

The short-term control of plasma concentrations of somatomedin C (SmC) in young chicks was examined by either surgical removal of the pituitary gland or by the administration of hormones which affect plasma concentrations of growth hormone (GH). As expected, removal of the source of GH by hypophysectomy reduced plasma concentration of GH, these being suppressed by 95.7% within 1 hour. Hypophysectomy was rapidly followed by reductions in the plasma concentration of SmC. For instance, plasma concentrations of SmC were decreased to 53% of pretreatment one hour following hypophysectomy. This suggests both that SmC has a short half life and that the release of SmC into the circulation is tightly coupled to the presence of pituitary hormone(s), presumably including GH. Sham surgery also decreased plasma concentrations of GH but were without effect on plasma concentrations of SmC. The short term control of plasma concentrations of SmC was also examined by the acute administration of hormones, which affect GH secretion in vivo. Injections of thyroxine or triiodothyronine decreased the plasma concentration of GH but were without effect on the plasma concentration of SmC. On the other hand, the administration of either glucagon or insulin decreased the plasma concentration of both GH and SmC. The present data suggest that plasma concentrations of SmC do not simply reflect the GH status in young chickens.

Animals↗

Induction of hepatic estrogen sulfotransferase expression by hypophysectomy in female rats.

We have examined the effects of hypophysectomy and treatment with thyroxine (T4) on enzyme activity and expression (as determined by immunoblot analysis) of members of the three principal sulfotransferase (ST) sub-families (phenol STs, PST; estrogen STs, EST; hydroxysteroid STs, HST) in cytosols prepared from female Wistar rat livers. The results demonstrate that in female rat liver cytosol, EST activity was decreased by treatment with T4, increased following hypophysectomy and that treatment of hypophysectomized animals with T4 also greatly reduced EST activity. T4 had no significant effect on PST or HST activity in normal animals, but it decreased HST activity in hypophysectomized rat liver cytosol. Immunoblot analysis of these cytosols with antibodies recognising HST and PST indicated that where changes in enzyme activity occurred they mirrored changes in enzyme protein expression. In normal adult female rat livers, EST protein is not expressed, and the small residual activity results predominantly from the action of HST. Hypophysectomy induced EST activity and the expression of EST enzyme protein in female rat liver cytosol, and T4 treatment of hypophysectomized animals reduced the activity to below normal levels without reducing the corresponding enzyme protein levels, indicating that T4 regulation of EST in females is via a post-translational mechanism.

Animals↗

Differential effect of hypophysectomy and growth hormone treatment on hepatic glucuronosyltransferases in male rats: evidence for an action at a pretranslational level for isoforms glucuronidating bilirubin.

The influence of growth hormone (GH) on 4-nitrophenol, bilirubin, testosterone, androsterone and estrone glucuronidation activities was studied in fully activated male rat hepatic microsomes. Sham-operated and hypophysectomized animals were injected with two different dosages of GH, mimicking either the male or female GH secretion pattern. Half the animals received thyroxine and cortisol in concentrations chosen to compensate for the lack of thyroid hormones and glucocorticoids in hypophysectomized rats. GH induced a decrease in several glucuronidation activities: bilirubin glucuronidation in both sham-operated and cortisol/ thyroxine-treated hypophysectomized rats in a dose-dependent manner, testosterone glucuronidation in hypophysectomized animals, and androsterone and estrone glucuronidation in cortisol/thyroxin-treated hypophysectomized rats. 4-nitrophenol glucuronidation was not affected by GH treatment. A hypothetical "feminizing" effect of GH (due to an almost continuous secretion) could not be invoked to explain these results, contrary to what has been observed elsewhere for other hepatic enzyme activities. Hypophysectomy altered all the activities tested, with bilirubin the most modified (a 200% enhancement). Restoration of control values was achieved in hypophysectomized animals with cortisol/thyroxine replacement together with a low dosage of GH (mimicking a male GH secretion pattern), except for androsterone glucuronidation activity where both GH and cortisol/thyroxine treatments reinforced the decreasing effect of hypophysectomy. Variations in protein amounts were correlated to variations in bilirubin, testosterone and androsterone conjugation activities induced by hypophysectomy and GH treatment. Reverse transcription-polymerase chain reaction (RT-PCR) mRNA analysis of bilirubin cluster isoforms or uridine diphosphate glucuronosyltransferase 1B1 (UGT1B1), UGT1B2 and UGT1B5 showed that GH controlled the different isoforms involved in bilirubin glucuronidation differentially at a pretranslational level.

Animals↗