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Plasma ACTH responses to cortisol infusion are similar in patients with primary hypoadrenalism and patients studied some years after bilateral adrenalectomy for Cushing's syndrome.

It has been suggested that the first-phase feedback of steroid feedback on ACTH secretion is abnormal in Cushing's disease patients studied after adrenalectomies. We have performed hydrocortisone infusions (100 mg over 2 h) in 15 patients who had previously undergone bilateral adrenalectomy for Cushing's disease. None had had any pituitary-directed therapy and none had a pituitary macroadenoma. Their responses were compared with a group of seven hypoadrenal patients. A significant rise in serum cortisol was observed between 5 and 10 min in both groups. The first significant fall in ACTH occurred between 30 and 45 min in both groups. There was no abnormality of first-phase feedback in the Cushing's group and our results do not therefore support previous speculation that such an abnormality provides evidence for a higher central nervous system (CNS) aetiology of Cushing's disease.

Adrenal Insufficiency↗

The effect of cyproheptadine and/or bromocriptine on plasma ACTH levels in patients cured of Cushing's disease by bilateral adrenalectomy.

Cyproheptadine and bromocriptine have been reported to be therapeutic in suppressing ACTH levels in Cushing's disease and Nelson's syndrome. However, there have been only scattered reports of their effect in suppressing raised ACTH levels found in patients cured of Cushing's disease by bilateral adrenalectomy. In order to assess whether these agents could prove beneficial in such patients we studied 12 patients previously treated with bilateral adrenalectomy alone for Cushing's disease before and after 3 weeks of cyproheptadine and/or bromocroptine therapy. All had raised plasma ACTH values but no patient had evidence of a pituitary macroadenoma. Plasma ACTH and cortisol were sampled 2-hourly for 24 h. Neither drug regime led to any change in plasma levels of cortisol for 24 h after a 20 mg dose of oral hydrocortisone. Plasma ACTH (mean +/- SEM) showed a small but significant overall reduction (523 +/- 45 vs 392 +/- 34 ng/l; P less than 0.05) while on bromocriptine alone (5 mg given at 0800 and 1800 h, n = 5). When each time point was analysed individually this reduction was significant at only five out of 13 time points. At 0400 h plasma ACTH (mean +/- SEM) was 758.4 +/- 298.1 vs 380.2 +/- 166.6; 0600 h, 795 +/- 288.7 vs 477.8 +/- 191.7; 1200 h, 266.8 +/- 106.2 vs 187.0 +/- 80.3; 1400 h, 470.0 +/- 239.0 vs 302.0 +/- 135.9; 1600 h, 548.6 +/- 262.5 vs 394.2 +/- 178.5 ng/l (P less than 0.05). There was no significant change in plasma ACTH during treatment with the combination of bromocriptine and cyproheptadine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Effect of adrenalectomy and dexamethasone treatment on testicular enzymes involved in carbohydrate metabolism.

The effect of adrenalectomy on specific activities of testicular hexokinase, 6-phosphofructokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and glycogen concentration have been studied. A general increase in specific activities of all enzymes was seen after adrenalectomy in rats of all ages studied. However, lactate dehydrogenase activity and glycogen concentration in pre-pubertal rats alone were depleted with no alteration in pubertal and adult animals. This was accompanied by increased prolactin titres, but gonadotrophins and testosterone were unaltered. Dexamethasone treatment returned all enzyme activities and hormonal profiles to normal.

Adrenalectomy↗

Influence of adrenalectomy on the developing rat thymus during peri-weaning period.

Adrenalectomy of 17-, 18- and 19-day-old male and female rats did not cause any changes in the weight of thymus 4 days later. Adrenalectomy on day 20 of age induced a significant hypertrophy of the thymus 4 days later. These results indicate that on day 20 of age, just before weaning, the thymus is under some inhibitory regulation by the adrenal gland.

Adrenal Glands↗

Effects of adrenalectomy and adrenal steroids on the uptake of serotonin in rat platelets.

Changes induced by adrenalectomy, triamcinolone treatment and deoxycorticosterone (DOC) treatment on the uptake of [3H]-serotonin into platelets were studied ex vivo, using rat platelets suspended in physiological medium. Adrenalectomy caused a decrease in active uptake of serotonin and an associated increase in apparent Km. Treatment of the adrenalectomized rats with triamcinolone (0.25 mg/kg), but not DOC (1.0 mg/kg) restored the active uptake of serotonin. At triamcinolone dose of 0.5 mg/kg, the serotonin uptake was raised to a level that was significantly higher than normal. Kinetic analysis of uptake data showed the apparent Km to be affected by both triamcinolone and DOC, while the apparent Vmax of uptake rate was increased by triamcinolone treatment.

Adrenal Cortex Hormones↗

Unexpected incidence of low blood pressure 2 years after unilateral adrenalectomy for primary aldosteronism.

1. Serial observations of blood pressure after unilateral adrenalectomy for aldosterone-producing adenoma revealed an incidence of hypotension (systolic BP less than fifth percentile for age- and sex-matched normal population) of 27% at 2 years, more than 5 times that predicted. 2. Serial observations of volume regulatory hormones showed significantly raised mean levels of plasma renin activity consistent with hypovolaemia. Significantly reduced mean aldosterone levels despite significantly raised mean plasma renin activity levels may reflect reduced responsiveness of the remaining adrenal. 3. Reduction of significantly elevated preoperative ANP levels to significantly reduced levels postoperatively is also in keeping with postoperative hypovolaemia. 4. A 50% reduction in plasma adrenaline after unilateral adrenalectomy might contribute to reduced noradrenergic activity (prejunctional beta-receptor) and reduced blood pressure, but plasma noradrenaline did not fall significantly postoperatively. 5. Postoperative levels of renin, aldosterone, adrenaline and noradrenaline were not significantly different between those who did, and those who did not, become hypotensive.

Adenoma↗

Response to unilateral adrenalectomy for aldosterone-producing adenoma: effect of potassium levels and angiotensin responsiveness.

1. Normokalaemic primary aldosteronism (PA) masquerades as 'essential hypertension', and 50% of patients with aldosterone-producing adenoma (APA) are normokalaemic at presentation to this unit. 2. Angiotensin-responsive (AII-R) APA is as common as angiotensin-unresponsive (AII-U) APA, and requires adrenal venous sampling for differentiation from bilateral adrenal hyperplasia (BAH). 3. From 1981 to 1992, 55 patients with APA underwent unilateral adrenalectomy and were followed up for at least 12 months postoperatively. Hypertension was cured in 55% and improved in the remainder. 4. Cure rate was lower (P < 0.001) in males (11/32, 34%) vs females (19/23, 83%), lower (P < 0.005) in patients over 45 years of age (13/33, 39%) vs those 45 years or younger (17/22, 77%), lower (P < 0.05) in AII-R APA (11/28, 39%) vs AII-U APA (19/27, 70%) and tended to be lower (not significant) in normokalaemic APA (7/17, 41%) vs hypokalaemic APA (23/38, 61%). 5. A higher proportion (P <0.001) of AII-R APA patients were males (23/28, 82%) vs AII-U APA (9/27, 33%), and a higher proportion were from the older age group AII-U APA 13/27, 48%; P < 0.05). Females with AII-U APA who were hypokalaemic had a very high cure rate (16/17, 94%). 6. Since unilateral adrenalectomy cures or improves blood pressure in normokalaemic and AII-R as well as in hypokalaemic and AII-U patients, all hypertensives should be screened for PA, and AII-R APA differentiated from BAH in proven PA.

Adrenal Cortex Neoplasms↗

Delayed adrenal insufficiency long after unilateral adrenalectomy: prolonged glucocorticoid therapy reduced reserved secretory capacity of cortisol.

A 51-year-old woman with Cushing's syndrome underwent unilateral adrenalectomy for left adrenal adenoma. After 7 years of prednisolone treatment (with some interruptions), followed by 4 years of total withdrawal from prednisolone treatment, she presented with hypotension, weight loss, general fatigue, nausea, hyponatremia and hypoglycemia. These clinical features together with a low response in the rapid adrenocorticotropic hormone test led to the diagnosis of acute adrenal insufficiency. Relatively low serum adrenocorticotropic hormone levels in the face of increased demand for cortisol during adrenal crisis suggested a disordered hypothalamic-pituitary function, indicating secondary adrenal insufficiency. This patient demonstrated the etiology of acute adrenal insufficiency long after unilateral adrenalectomy in association with subsequent glucocorticoid therapy. A reduction in the reserved secretory capacity of cortisol after prolonged prednisolone treatment was considered to have induced secondary adrenal insufficiency, even after 4 years of total withdrawal from prednisolone.

Acute Disease↗

Laparoscopic left adrenalectomy: a new approach.

Left adrenalectomy has been performed previously via anterior, posterior, loin or thoracoabdominal approaches. In the classical transabdominal approach the left adrenal gland is resected following either mobilization of the spleen with the tail of the pancreas or after entering the lesser sac, mobilizing the inferior border of the pancreas off the adrenal gland. This report describes laparoscopic left adrenalectomy, in a patient with Conn's syndrome, performed by a new approach via the root of the left transverse mesocolon.

Adrenalectomy↗

Enhanced cochlear acoustic sensitivity and susceptibility to endotoxin are induced by adrenalectomy and reversed by corticosterone supplementation in rat.

Glucocorticoid receptors are widely distributed in the cochlea but their role remains poorly known. Previous studies provided contradictory reports on a possible cochlear acoustic hypersensitivity induced by adrenal insufficiency, while several experiments agree on a significant action of glucocorticoid receptors in adverse conditions such as acoustic trauma and restraint stress. The present experiments confirmed a cochlear acoustic hypersensitivity induced by adrenalectomy and reversed by corticosterone supplementation. These observations point to a significant role of corticosteroids in basal cochlear functioning. The glucocorticoids are known to be essential for limiting and resolving inflammatory processes. The endotoxin Escherichia coli lipopolysaccharide is widely used to induce inflammatory reactions. However, in various organs several toxic processes of this endotoxin are not influenced by glucocorticoids. From previous experiments on the cochlea there is no evidence that glucocorticoids are an essential factor against endotoxin cochlear toxicity. In the present experiments it was found that adrenalectomy greatly increased the cochlear susceptibility to endotoxin; the effect was reversed by providing corticosterone supplementation. This shows the essential role of corticosterone in this cochlear inflammation model. In previous studies local administration (at the cochlear base) of endotoxin was used and losses of cochlear acoustic sensitivity were found predominantly at high frequencies; in contrast, the systemic injection used in this study produced a cochlear loss of acoustic sensitivity at all frequencies, indicating a uniform cochlear sensitivity to the toxic effects of endotoxin.

Acoustic Stimulation↗

Adrenalectomy of rats results in hypomyelination of the central nervous system.

The effect of adrenalectomy on CNS myelin accumulation was investigated to determine whether glucocorticoids play a role in regulating myelination. When 14-day-old rats were adrenalectomized and sacrificed 7-8 days later, the amount of bulk-isolated myelin in whole brain, as expressed per gram wet weight of brain or per milligram DNA-phosphate, was reduced to about 75% that of sham-operated controls. Both brain weight and DNA content were unchanged by adrenalectomy. Examination of individual brain regions also revealed decreased amounts of myelin in adrenalectomized animals. Brain glycerol 3-phosphate dehydrogenase specific activity was reduced in adrenalectomized animals to 40-60% that of controls, and serum corticosterone levels were less than 0.6% of control levels. The amount of cerebral myelin in animals adrenalectomized on day 21 and sacrificed 9 days later was not significantly reduced. This suggests a possible role of glucocorticoids during the early period of rapid myelination.

Adrenalectomy↗

Adrenalectomy attenuates stress-induced elevations in extracellular glutamate concentrations in the hippocampus.

Glucocorticoids and stress have deleterious effects on hippocampal cell morphology and survival. It has been hypothesized that these effects are mediated via an excitatory amino acid mechanism. The present study was designed to evaluate the effects of acute stress on the extracellular levels of glutamate in the hippocampus and to determine if adrenalectomy modifies this response. Rats were adrenalectomized or sham-adrenalectomized and implanted with microdialysis probes in the CA3 region of the hippocampus. Three days later rats were subjected to an acute 1-h period of immobilization stress. Stress significantly increased extracellular glutamate levels in the sham-operated rats, which peaked at 20 min following the initiation of stress. Extracellular glutamate levels also increased immediately following the termination of stress. In the adrenalectomized rats there was a 30% decrease in basal extracellular concentrations of glutamate and a marked attenuation (-70%) of the stress-induced increase in extracellular glutamate levels. Extracellular concentrations of taurine were not modified by adrenalectomy and did not change in response to stress. These results suggest that glucocorticoid-induced elevations in extracellular glutamate concentrations may contribute to the deleterious effects of stress on hippocampal neurons.

Adrenalectomy↗

Adrenalectomy abolishes antagonism of alpha-adrenoceptor-mediated hypotension by a beta-blocker in conscious rats.

1. The effects of a single bolus injection of propranolol, atenolol or ICI 118,551, non-selective beta-, selective beta 1- and selective beta 2-adrenoceptor antagonists, respectively, on mean arterial pressure (MAP) and plasma catecholamine concentrations were examined in seven groups of conscious and unrestrained adrenalectomized rats receiving a continuous infusion of the alpha-adrenoceptor antagonist phentolamine. In all rats adrenaline was undetectable in the plasma four days after adrenalectomy. 2. In the first three groups, phentolamine significantly decreased MAP and increased the plasma concentrations of noradrenaline. The injection of propranolol, atenolol or ICI 118,551 in Groups I, II and III, respectively, caused a small increase in MAP and a small, but not significant, decrease in plasma noradrenaline concentrations. 3. Groups IV, V and VI were given a continuous infusion of adrenaline for 1 h prior to the infusion of phentolamine, followed by a bolus injection of propranolol, atenolol or ICI 118,551, respectively. Group VII was treated similarly to IV, but was also given daily cortisone replacement after adrenalectomy. Adrenaline slightly, but not significantly, decreased MAP while phentolamine significantly decreased MAP and increased plasma noradrenaline concentrations in all groups. A subsequent injection of a beta-blocker caused a significant increase in MAP in each group and a slight decrease in the plasma level of noradrenaline which reached statistical significance in group VII. The pressor effect of propranolol was significantly greater in the cortisone-treated rats (Group VII) than in Group IV. 5. The results suggest that adrenaline and adrenocortical steroids are both involved in the antagonism of alpha-adrenoceptor-induced hypotension by a beta-blocker.

Adrenal Glands↗

Increase in vascular permeability produced in rat airways by PAF: potentiation by adrenalectomy.

1. The effect of bilateral adrenalectomy on the sensitivity of blood vessels in rat airways to mediators that increase vascular permeability was examined. 2. An increase in vascular permeability was induced by intravenous platelet activating factor (PAF, 50, 100, 500, 1000 ng kg-1) and measured by quantifying the extravasation of Evans blue dye. 3. PAF consistently increased the amount of Evans blue extravasation in the larynx, trachea, main bronchi and intrapulmonary airways in sham-operated rats. 4. The magnitude of this extravasation was significantly greater in the larynx (P less than 0.05), trachea (P less than 0.05) and main bronchi (P less than 0.05) of the adrenalectomized rats than it was in these tissues of the sham-operated rats. 5. When adrenalectomized rats were given subcutaneous dexamethasone (0.2 mg kg-1 4 h before PAF) the amount of plasma extravasation produced by PAF was decreased to the level of the sham-operated rats. 6. We conclude that adrenalectomy potentiates the increase in airway vascular permeability induced by PAF in rats and that this effect may be due to the depletion of endogenous corticosteroids.

Adrenalectomy↗

Concomitant coronary artery bypass grafting and adrenalectomy for pheochromocytoma.

We report the first case of concomitant coronary artery bypass grafting (CABG) and adrenalectomy for pheochromocytoma. Which lesion to correct first and staging of the corrective procedures are highly controversial issues. Issues concerning pre- and intraoperative control of hemodynamic instability from catecholamine release are discussed. Preoperative alpha and beta blockade permitted excellent hemodynamic control in the operating room. Operative and postoperative courses were uneventful and the patient had complete resolution of his angina and hypertension. We conclude that concomitant CABG and adrenalectomy is the preferred approach when pheochromocytoma and symptomatic coronary artery atherosclerosis coexist.

Adrenal Gland Neoplasms↗

Need priorities of adrenalectomy patients as perceived by patients, nurses, and physicians.

Patients in this study identified needs they considered important. Perceived need priorities of adrenalectomy patients need to be identified and met both pre- and postoperatively by health team members. Patient-centered nursing and medical conferences should be arranged to provide comprehensive patient care. Establishment of guidelines, based on need priorities perceived by the patient, will provide a master care plan which can assist nurses and physicians in meeting patient needs. These guidelines are important since patients need not only an immediate care plan, but also a long-term plan of care designed to meet individual needs and ever-changing problems of the long-term illness. The study findings show that patients, nurses, and physicians differ in their perception of need priorities of adrenalectomy patients. Nurses and physicians must take heed of patient concerns. Nurses, especially, must realize the needs of the patient in order to provide support, counseling, and education. The necessity for total awareness of patients' needs and perceptions is illustrated by one cancer patient's comments: "Although the disease was diagnosed early and responded successfully to treatment, there was a numbness and fear, the cold chills that accompanied the awareness of the diagnosis and later the altered perception of life, of friends and associates that grew out of the realization that death was never far away. "A human organism with a malignant neoplasm is more than a body with a disease. It is also a reacting individual who has feelings about his illness, and these feelings influence the way he perceives his medical personnel and utilizes his advice and care." It is important that all members of the health team acquire a better understanding of the various need theories and the importance of perceiving the needs of patients as the patient perceives them. In addition, it is essential for health team members to continually refer to the relevant literature concerning needs to improve the quality of total patient-family care.

Adrenalectomy↗

Effect of hypophysectomy and adrenalectomy on 5-hydroxytryptamine uptake by rat hypothalamic synaptosomes and blood platelets.

The effect of adrenalectomy and hypophysectomy on 5-HT uptake by rat platelets and hypothalamic synaptosomes taken from the same animal was studies. The experiments were performed 1-2 weeks after the operations of the shamoperations. After adrenalectomy a significant decrease of 25% in 5-HT uptake by platelets was noted. In synaptosomes there was a similar trend, but the decrease was not significant. After hypophysectomy a significant 25% decrease in 5-HT uptake was observed both in platelets and in synaptosomes. These results suggest that corticosteroid hormones might mediate adaptive changes of 5-HT uptake both in synaptosomes and in blood platelets. Blood platelets have been used as a peripheral model of serotoninergic nerve terminal in studies concerning physiology of monoamines systems. But the present results suggest that also in some pathological conditions changes in platelet biochemistry could reflect those in the CNS neurones.

Adrenalectomy↗

Adrenalectomy of sheep: a novel technique.

A rapid technique for adrenalectomy of sheep was developed. Bilateral adrenalectomy was performed in a single stage operation by inducing ischaemia with latex rings of the type used commonly for the castration of lambs and calves. The success of the technique was demonstrated by failure of exogenous ACTH to increase circulating cortisol concentrations. Adrenal steroid replacement was used to maintain the sheep during the post-operative period (cortisol 0.25 mg.kg-1, deoxycorticosterone acetate 0.05 mg.kg-1). Adrenalectomised sheep were maintained for up to 20 days without glucocorticoid, provided a lowered dose of mineralocorticoid was administered (0.04 mg.kg-1 x day-1). Adrenalectomised sheep had significantly (P < 0.007) lower packed cell volume (23.75%) than normal sheep (31.24%), across a broad range of cortisol concentrations (0 to 734 ng/mL), indicating that plasma cortisol may not reflect true blood concentrations when drawing comparisons between adrenalectomised and normal sheep.

Adrenalectomy↗