Hypophysectomy

Radiosurgery for Functional Disorders and Epilepsy

Alfredo Quiñones-Hinojosa MD , in Schmidek and Sweet: Operative Neurosurgical Techniques , 2022

Hypophysectomy past Stereotactic Radiosurgery

Recently, SRS and specially GKR have been used in this indication. Lars Leksell initially targeted the medial thalamus for hurting related to malignant tumors. 105 In that location are, to date, very few published data on this indication. The target was additionally inverse, based on the observations made past Liscak et al. 106 who used the pituitary gland in patients with bone metastasis; at 1 to 2 years, all patients experienced an important benefit in the absence of complications. Moreover, Hayashi et al. 107 (Fig. 97.4) used a maximal dose of 160 Gy and targeted the pituitary gland. The results were encouraging, with pain freedom without complications.

Mainly, the results after SRS 108 are efficacy in a few days, no recurrence during brusque-term follow-up, no difference between hormodependent and nonhormodependent cancers, no MRI change, and no hormonal and visual side result.

ESTROGENS AND STRIATAL CHOLINERGIC FUNCTION

C. EUVRARD , J.R. BOISSIER , in Steroid Hormone Regulation of the Encephalon, 1981

Effect of hypophysectomy or pituitary gland transplantation on the apomorphine-induced increment in striatal ACh levels

Hypophysectomy did not change the striatal ACh levels, nor did it modify the increment in ACh concentrations due to apomorphine ( Fig. 4). In dissimilarity to intact animals, in hypophysectomized rats moxestrol was completely ineffective in blocking the apomorphine-induced increase in striatal ACh levels (Fig. 4). In the hyperprolactinaemic pituitary transplanted rats (serum PRL levels: 22 ± 3 ng/ml in sham operated rats and 318 ± 45 ng/ml in pituitary transplanted rats) the apomorphine effect on striatal ACh levels was significantly reduced as compared to sham operated rats whereas the baseline striatal ACh levels were similar in sham operated and pituitary transplanted rats (Fig. 4).

Fig. 4. Effect of apomorphine on striatal ACh levels in rats following modifications of their hormonal condition.

Saline or apomorphine was injected into intact, hypophysectomized or hyperprolactinaemic pituitary transplanted male rats and the animals were killed 45 min after. Values are expressed as the mean ± SEM of results obtained with groups of 7 rats. The indicated percentages and p values are for apomorphine versus apomorphine in pretreated (moxestrol or pituitary transplanted) rats; ✠ and ✠✠ represent the significance for apomorphine versus saline treatment at the level of p < 0.05 and p < 0.01 respectively.

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Neurosurgical anaesthesia

Jonathan Thompson undefined , in Smith and Aitkenhead's Textbook of Amazement , 2019

Pituitary surgery (hypophysectomy)

The pituitary fossa is most usually approached through the nose and sphenoid sinus (trans-sphenoidal). Less commonly it requires a frontotemporal craniotomy for large suprasellar tumours. The bulk of pituitary adenomas are not-functioning and cause force per unit area symptoms, usually on the optic chiasm leading to a bitemporal hemianopia. Nevertheless, there may exist preoperative endocrine abnormalities such as acromegaly or Cushing'due south affliction. Acromegalic patients who present for pituitary surgery may pose difficulties in tracheal intubation and are at risk of obstructive slumber apnoea.

Glucocorticoid replacement is required in the immediate perioperative menstruum; mineralocorticoid requirements increment only slowly over the subsequent days. Diabetes insipidus may present in the immediate postoperative period and requires stabilisation with vasopressin until the caste of the imbalance is known. Information technology ordinarily resolves over the outset few days. If the nasal approach is used, a pharyngeal pack should be inserted and the airway protected to prevent aspiration of claret and CSF.

Biomedical Research Techniques

Jerald Silverman , in The Laboratory Rabbit, Guinea Sus scrofa, Hamster, and Other Rodents, 2012

Hypophysectomy

Hypophysectomy requires strict attention to technique equally the operator is working close to the jugular veins and numerous nerves. The parapharyngeal technique is the method most often used in hamsters and the surgical procedure noted herein is that previously described by Silverman (1987). The anesthetized animal is placed in dorsal recumbency with the brute's tail toward the operator. An endotracheal tube is not commonly used. The animal'due south body, and particularly its head, must be well secured so that it does not move during surgery. A 1.5-cm incision begins in the mid-cervical area and extends anteriorly nearly to the mandibular symphysis. The skin and mandibular salivary glands are retracted, exposing the trachea, sternohyoid, and omohyoid muscles. Using two iv.5-inch fine forceps, the muscles are separated and then retracted. The trachea is advisedly retracted, simply merely when needed to obtain meliorate visualization of the underlying cranium. A dental scraper is used to remove about a 1-cm circle of periosteum from the ventral cranium immediately dorsal to the trachea. This will reveal a faint blueish suture line betwixt the basisphenoid and occipital bones, which will be the area for subsequent trephining. The os can now exist removed by first gently scoring with a minor trephine and then using a second trephine to remove the bone or by using a dental drill with a burr. The pink-colored gland is now visible and information technology tin exist sucked out using a 16–18-gauge needle (with a blunted terminate) and 10   lb of vacuum pressure. Any bleeding is controlled with cotton-tipped or oxidized cellulose swabs. The pars distalis of the hamster pituitary extends forwards and laterally making information technology somewhat difficult to fully remove and the gland oft separates into numerous pieces during removal (Knigge, 1954). Postsurgical analgesics are routinely provided and a ten% glucose solution, given orally, will assistance foreclose hypoglycemia. A detailed description of parapharyngeal hypophysectomy in the mouse is available (Hoff et al., 2006).

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Proliferative Diabetic Retinopathy

Andrew P. Schachat MD , in Ryan's Retina , 2018

Pituitary Ablation

Building on the fundamental discovery of Biasotti and Houssay 99 that hypophysectomy reduced the severity of diabetes in pancreatectomized dogs, Luft and coworkers 100 carried out hypophysectomy in the hope of ameliorating the vascular complications of diabetes. Further impetus was provided by Poulsen's written report 100,101 of remission of DR in a woman with postpartum anterior pituitary insufficiency (Sheehan syndrome). Over the next 25 years, various types of pituitary suppression were used, ranging from external irradiation to transfrontal hypophysectomy. A consensus adult amidst advocates of these procedures that complete or nearly complete suppression of inductive pituitary function (pituitary ablation) produced rapid comeback in eyes with severe NPDR and actively growing new vessels not however accompanied by extensive fibrous proliferations. Although only ii randomized trials take been reported, 101 both small and neither in itself compelling, the weight of evidence supports the belief that it had some beneficial effect. Particularly persuasive are comparisons between patients in whom trans-sphenoidal implantation of radioactive yttrium was followed by complete or about complete anterior pituitary suppression and similar patients in whom little or no suppression was achieved. Substantially better outcome was observed in the former group. 102 Boosted support is provided by a nonrandomized comparison of eyes with very extensive new vessels and IRMA, in which outcome was amend in the eyes of patients undergoing pituitary ablation than in similar eyes receiving photocoagulation or no treatment. 103 Pituitary ablation is now simply of historical interest considering laser photocoagulation and anti-VEGF therapy are both far more effective and also free of the many substantial disadvantages of inducing and living in the hypopituitary country with concomitant diabetes (e.thou., operative and immediate postoperative risks, increased susceptibility to severe insulin reactions, need for continuing replacement of adrenal corticosteroids, sterility).

The favorable effect of pituitary ablation on retinopathy is thought to be mediated by suppression of growth hormone activity and effects on insulin-like growth factor 1 (IGF-1). 104 Daily subcutaneous injections of a genetically engineered growth hormone receptor antagonist, pegvisomant, accept been given for 3 months in 25 patients with non-high-risk PDR. Regression of new vessels did non occur in any patient, although the serum level of IGF-ane, a growth factor whose secretion is stimulated by growth hormone, did decrease an boilerplate of 55% compared to baseline levels. 105 In a pocket-size randomized clinical trial, multiple daily subcutaneous injections of octreotide, a somatostatin analog that inhibits both growth hormone and insulin-like growth gene, were given to xi patients with astringent NPDR or not-high-risk PDR. During fifteen months' follow-up, one out of 22 of these patients' optics required besprinkle laser photocoagulation compared to ix out of 24 eyes of 12 patients randomly assigned to an untreated control grouping. 106 However, larger clinical trials of somatostatin analogs were not found to be constructive.

Effects OF ANDROGENIC AND ADRENOCORTICAL STEROIDS ON HYPOTHALAMIC AND PREOPTIC CATECHOLAMINE NERVE TERMINALS AND ON THE SECRETION OF ANTERIOR PITUITARY HORMONES

K. ANDERSSON , ... J.-Å. GUSTAFSSON , in Steroid Hormone Regulation of the Brain, 1981

Studies in hypophysectomized male person rats

Hypophysectomy was performed according to the transaural arroyo ii-3 weeks before the experiment. ACTH 1-24 or saline was injected into the lingual vein in a dose of 100 μg/kg at the same time every bit the H 44/68 was injected (250 mg/kg, i.p., 2 h earlier killing). In one grouping of animals adrenalectomy was performed 24 h before the injection of ACTH one-24. No furnishings of CA levels in the various regions could be observed after ACTH 1-24 treatment. In this experiment it could be confirmed that ACTH 1-24 selectively increased NA turnover in the SEL and in the MPZ ( Fuxe and coworkers, 1978a; Andersson and colleagues, 1980). Furthermore, information technology could be demonstrated that this increment induced by ACTH was not blocked past prior adrenalectomy indicating that this activity was independent upon the presence of adrenocortical steroids. These results give farther support to the existence of an inhibitory noradrenergic mechanism regulating CRF neurons within the median eminence. Furthermore, the fact that this treatment did not alter DA turnover in the LPZ once again suggest that the DA terminals in this area are not involved in the regulation of CRF secretion.

Still, the ability of ACTH 1-24 to reduce NA turnover in the PA FM was blocked by prior adrenalectomy (Andersson and colleagues, 1980). These results suggest that in order to reduce NA turnover in the PA FM, ACTH requires the presence of adrenocortical steroids. The fact, however, that in the 4 week adrenalectomized rat a reduction of NA turnover was observed in this region indicates that a chronic hypersecretion of ACTH can by itself produce a reduction of NA turnover in this surface area in the absence of adrenocortical steroids. The results support the view that the NA nerve terminals within the PA FM can regulate the activity in the vasopressin pathways, which may correspond ane of the CRF pathways.

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ENZYMIC Action IN THE ISLETS OF LANGERHANS

L. ARVY D.Thousand., D.Sci. , in Histoenzymology of the Endocrine Glands, 1971

EXPERIMENTAL VARIATIONS

Hypophysectomy scarcely modifies the element of group i phosphatase of the islet ( Dempsey, 1948) and i handling with alloxan does not decrease the alkaline metal phosphatase histochemically detectable in the α-cells of rat (Cavallero and Solcia, 1964). Alloxan is β-cytotoxic in rat and so islets composed most exclusively of α-cells are obtained, which dissimilarity clearly with the exocrine pancreas because of their strong alkaline phosphatase activity (Soulairac and Desclaux, 1951; Solcia, 1963; Petkov et al., 1965).

Treatment with benzylthiouracil causes a decrease in alkaline metal phosphatase activity (Soulairac and Desclaux, 1951).

Insulin treatment causes a noticeable decrease in histochemically detectable alkaline metal phosphatase activeness in the α-cells of rat, fifty-fifty though the number of α-cells does non vary, for this enzyme can only be detected in nigh four·5% of them. Handling with one·5 IU insulin for three days causes disappearance of the alkaline phosphatase from the islets (Verne and Petkov, 1961).

Fasting, on the other mitt, causes an increase in alkaline phosphatase in rats. The enzyme is then present in almost of the α-cells. Injection of glucose similarly increases the alkaline phosphatase of the α-islet tissue. The observations of Verne and Petkov (1961) are summarised in Table 43.

TABLE 43. VARIATIONS IN THE ALKALINE PHOSPHATASE ACTIVITY OF THE PANCREAS CELLS OF RAT

Treatment Normal rat 2½ 60 minutes after 0·5 IU insulin 15 IU insulin (3 days) 2½ hour afterwards 5 ml 5% glucose 5 ml 5% glucose (3 days) Fasted 800 γ glucagon (in four doses)
% cells with alkaline phosphatase fourteen·5–15 4·5 1·5 xvi–17 iv–6 21 2·two

(from Verne and Petkov, 1961)

Copyright © 1961

Verne and Petkov (1961) have also reported that in rat the α-cells lose their histochemically detectable glycerophosphatase activity (Table 43), in the hours or days, following the administration of glucagon (600–3000 γ i/p). Thus the enzymic action seems to evolve very closely with the insular secretory action. Injection of glucagon puts the α-cells in a resting state while insulin exhausts them. Awarding of quantitative chemical micromethods to the microdissected islets of rat shows that assistants of glucagon causes a clear increase in the alkaline phosphatase activity (from 0·56±0·09 to 0·94±0·thirteen). Withal, the alkaline phosphatase action of the liver and of the exocrine pancreas are stimulated simultaneously, so that islet glycerophosphatase hyperactivity is perhaps not exactly conditioned by the subtract in glucagonogenesis instigated by the exogenous glucagon (Täljedal et al., 1966).

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Cushing Disease

John D.C Newell-Price , in The Pituitary (Fourth Edition), 2017

Furnishings of ACTH on Corticosteroid Secretion and the Adrenal Gland

Hypophysectomy results in adrenal cortex atrophy that is restored past administration of ACTH. Thus, in vivo, ACTH is the predominant if not exclusive trophic gene for the adrenals. Prolonged in vivo stimulation with chronic ACTH administration or oversecretion somewhen leads to increased total adrenal protein and RNA synthesis. The resulting adrenocortical hyperplasia participates in the amplified response of the chronically stimulated gland, and the weight of each gland is profoundly increased.

Steroidogenesis in the zona fasciculata and the zona reticularis of the adrenal cortex is regulated predominantly by ACTH, and patients with Cushing disease show bilateral adrenocortical hyperplasia with widening of these regions. ACTH binding to the MC2 receptor in the adrenal cortex induces an immediate secretion of glucocorticoids, androgens, and mineralocorticoids. The primary mediator of ACTH action is military camp and camp-dependent protein kinase.

Considering low amounts of steroid are stored in the gland, increased secretion is a reflection of increased synthesis. ACTH primarily acts to increase the rate-limiting step of steroid synthesis (conversion of cholesterol to pregnenolone) by enhancing accessibility of cholesterol to substrate-bounden site of cytochrome P450. In the long term, ACTH action also induces expression of primal steroidogenesis enzymes [196,197].

In dissimilarity with many hormones, chronic adrenocortical stimulation past ACTH causes upregulation of its receptor (MC2R). This long-recognized phenomenon had been attributed to a "trophic" effect of ACTH, and adrenocortical cells exposed to ACTH in vitro larn an increased number of ACTH receptors and an increased rate of protein Gs expression [198–200]. Thus, binding of ACTH and the transducing apparatus are both amplified, explaining the higher sensitivity and the greater response potential of chronically stimulated cells.

An autocrine network mediated by ACTH-induced growth factors operates on adrenocortical cells. Insulin-like growth factor-1 (IGF-ane) is secreted [201,202] and acts on its own receptors to stimulate differentiated functions of adrenocortical cells [203,204]. In dissimilarity, transforming growth factor-β (TGF-β) exerts inhibitory furnishings, its receptors also regulated past ACTH. Moreover, ACTH favors release of angiogenic factors such every bit basic fibroblast growth gene (bFGF) and IGF-two, thus stimulating the growth of the adrenals and of their vascular organisation.

In comparison with normal cells, hyperplastic adrenocortical cells of Cushing disease patients accept particular qualities: (1) they are more than sensitive to depression doses of ACTH and (ii) their response to ACTH stimulation is college and longer. If Cushing disease is defined every bit a set-indicate defect at the pituitary level, increased responsiveness of chronically stimulated adrenal glands may lower the amount of ACTH required to maintain the same caste of cortisol oversecretion. Macerated ACTH secretion would thus occur in parallel with adrenal hyperresponsiveness, such that plasma ACTH may be measured at the lower cease of the reference range. This reciprocal interaction between the adrenals and the pituitary adenoma may explicate why no practiced correlation is found between plasma ACTH levels and the level of cortisol overproduction in patients with Cushing disease [205].

Mechanisms of adrenal androgen secretion grossly parallel those of cortisol. Thus, levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and Δ-4-androstenedione are elevated in Cushing disease [206]. Peripheral transformation to testosterone and dihydrotestosterone may lead to a moderate state of androgen backlog in females [207]. Dissociation between cortisol and adrenal androgens is observed, however, when patients resume normal corticotroph function later successful pituitary surgery. DHEAS may remain suppressed for months or years after plasma cortisol has normalized [206].

The action of ACTH on adrenal mineralocorticoids is more complex. In the zona glomerulosa, ACTH acutely stimulates aldosterone release [208]. Yet this activity is only transient, since increased concentrations of cortisol in the adrenal cortex inactivate cytochrome P450 eleven-β-corticosterone methyl oxidase. In contrast, in the zona fasciculata and reticularis, the stimulatory activity of ACTH is permanent. Thus 11-deoxycorticosterone (Medico), corticosterone, and oft eighteen-OH-DOC, are elevated, whereas aldosterone and 18-OH-B are normal or slightly suppressed in parallel with low plasma renin activity. The concentration of plasma zona fasciculata mineralocorticoids DOC is straight correlated to that of ACTH and participates equally one determinant in the mechanism of high blood pressure [208]. In addition, when cortisol is stimulated at sufficient levels to saturate the renal-protective HSD11B2 enzyme, cortisol-induced mineralocorticoid hypertension results [209].

Various physiologic agents may also act as possible regulators of ACTH action at the adrenal level or fifty-fifty as regulators themselves. Angiotensin II, serotonin, and interleukins have credible stimulatory actions [210]. Atrial natriuretic cistron inhibits the action of ACTH both on the zona glomerulosa and the zona fasciculata [211]. Peptides with anti-ACTH action (corticostatins) have been isolated from rabbit lung and peritoneal neutrophils, which are unrelated to POMC [212].

Due north-terminal fragment, γ3-MSH, β- and γ-LPH, β-MSH, α-MSH, and β-endorphin exert some issue on adrenal secretions [213–216]. In comparing with ACTH, much higher concentrations were required, raising uncertainty almost their significance [217]. Aldosterone-stimulating activity of the N-final fragment, β-LPH, β-endorphin, β-MSH, α-MSH, and γ3-MSH has been reported. Specific receptors to Lys-γ3-MSH have been described in the rat adrenal [218] where it would deed essentially equally a synergic molecule with ACTH. At that place is no evidence for these peptides having meaningful clinical relevance, primarily because of the weak intrinsic action of the peptides, and also because peptides such as γ3-MSH and β-MSH are not usually establish within normal or tumoral human pituitaries [89,219].

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Growth Hormone and Somatomedin

Kerstin Hall , Rolf Luft , in Advances in Metabolic Disorders, 1974

A In Animals

Post-obit hypophysectomy somatomedin disappears from rat serum with a half-life of 3–5 hours ( Daughaday et al., 1968), and the activity is restored past assistants of growth hormone. This response to growth hormone comes late, and elevation levels of somatomedin are reached only after 8–12 hours (Daughaday et al., 1968). Rats with growth hormone-secreting tumors showed increased levels of somatomedin, which were not influenced by the addition to the medium of specific antibodies to growth hormone. Therefore, it seems unlikely that the growth hormone and somatomedin molecules have a major core in mutual.

Farther evidence for the separate nature of somatomedin and growth hormone comes from a bizarre source. Subcutaneous implantation of the parasitic tapeworm Spirometra mansonoides induced growth in hypophysectomized rats during 4–6 weeks (Steelman et al., 1970). No significant increase in the levels of growth hormone could be seen, and the levels of somatomedin were elevated. Furthermore, serum from such rats stimulated cartilage growth after in vivo administration to other hypophysectomized rats. The growth-stimulatory effect of the tapeworm was lost subsequently some weeks, and at this fourth dimension the somatomedin activity was likewise gone (Garland et al., 1971; Daughaday and Garland, 1972). It seems, therefore, that other factors than growth hormone are able to induce somatomedin-like activity.

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Surgical Interventions for Hurting

Daniel Chiliad. Aghion , Garth Rees Cosgrove , in Chronic Hurting and Brain Abnormalities, 2014

Hypophysectomy

In 1952, hypophysectomies were performed for palliation from intractable pain related to metastatic carcinoma. Treatment for this disease entity has evolved tremendously over the past decades, but widespread acceptance for hypophysectomies lasted over 30 years and the indications for such a procedure broadened. Every bit a better agreement of hormones and their result on cancers such as chest and prostate cancer developed, surgery to remove target hormone glands such as the ovaries, adrenal glands, or even function or all of the pituitary gland began in attempts to go along the patient'due south cancer at bay. The results of this were mixed and sometimes life threatening complications, such as addisonian crisis ensued in some cases, but a marked effect on hurting relief was noticed. Open hypophysectomies transitioned to transsphenoidal approaches in the 1960s and this provided for a much less morbid surgical approach. Stereotactic radiofrequency and cryotherapy hypophysectomies were developed as well using radiographically guided instruments into the sella via a transsphenoidal arroyo. Though pain was usually only a secondary side consequence of the procedure, patients connected to report immediate and long lasting hurting relief after undergoing their surgery. Also in the 1960s, functional hypophysectomy for prostate carcinoma was attempted using brachytherapy with stereotactically implanted yttrium 90 with good pain relief. Additionally, in the late 1960s and 1970s stereotactic chemic ablation of the pituitary was performed with ethanol. It wasn't until the 1970'due south when the focus of reports on hypophysectomy focused primarily on hurting relief and non the effect on tumor control. Fracchia et al reported on a serial of 203 patients with advanced stage breast cancer treated with various forms of hypophysectomy, and 180 of 203 had pain relief with the procedure, although only 68 patients had no objective tumor response. The machinery of pain control later on hypophysectomy was initially viewed as a issue of tumor shrinkage, and removing hormonal stimulation led to an overall decrease in size of the tumor burden, thereby causing less pain. Equally time passed, however, information technology was noticed that pain relief was achieved in not-hormone responsive tumors in the absence of clinical improvement. No identifiable pituitary hormone was known as a pain mediator, but it wasn't until 1984 that Ramirez and Levin suggested that the paraventricular nucleus (PVN) in the hypothalamus may be the key anatomic locus for pain command. Projections from the PVN are known to innervate the spinal dorsal horn, perimesencephalic grayness, and other structures known to be of import hurting-modulating centers. Thus, the hypothalamus may in-fact be the fundamental to the efficacy of hypophysectomy but information technology is merely rarely performed today.

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